Cancer.Net Podcast

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Brian Shuch, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta (Monty) Pal.

Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck.

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb and Exelixis.

View full disclosures for Dr. Shuch, Dr. Agarwal, Dr. Grivas, and Dr. Pal at Cancer.Net.

Dr. Shuch: Hi, I'm Dr. Brian Shuch from UCLA's Institute of Urologic Oncology. And I'm really thrilled to moderate today's Cancer.Net podcast on GU clinical trials. I'm joined today by Dr. Neeraj Agarwal from Utah's Huntsman Cancer Center, Dr. Petros Grivas from the University of Washington's Fred Hutch Cancer Center, and Dr. Sumanta Pal from the City of Hope Cancer Center. Thanks for being here today, and we'll jump in to discuss 3 clinical trials in the urologic cancer space, one for prostate, one for bladder, and one for kidney cancer. Let's discuss some of the goals of clinical research first, okay? Neeraj, can you let us know what is the purpose of a clinical trial, and the ultimate goal?

Dr. Agarwal: All these clinical trials aim to identify better treatments with the hope that the treatment will be safe and effective. An ultimate goal for all the clinical trials is to get approval [from the FDA for the routine use of the new treatments being tested.] I'd like to add, that the way I explain this to my patient, a clinical trial is the only way I can get cutting-edge therapy for my patients in my clinic without having to wait for many years for FDA approval of those drugs.

Dr. Shuch: Petros, it seems that patient engagement is really essential to this type of clinical research. What is the patient's role here, and what can they expect by participation in a clinical study?

Dr. Grivas: They can directly help [the research team] define better treatments and also improve existing therapies. And they can do that by either participating in clinical trials directly, and can also help us find the clinical questions. And the patient advocate groups are helping us do that by giving us input how to design clinical trials. And, of course, a number of trials that we're conducting are focusing on disease prevention or treatment of the cancer. And I think the patient's role overall is critical in every patient who's asked their provider about clinical trials.

Dr. Shuch: So Monty, for your patients, how do you ensure patients are safe when they participate on these types of trials?

Dr. Pal: Safety is our primary concern when conducting a research study. The patients are taking risks by participating, and these risks should be very clearly delineated in the context of a consent form. It's really critical that we, as investigators, perform very close monitoring in association with our patients. But we also have very intensive oversight of our clinical trials by independent monitoring committees, by the drug companies, and even the FDA. Now, trials can actually be closed early if there are safety concerns that emerge, or if drugs don't appear to be effective. Keep that in mind.

Dr. Shuch: Got it. It's reassuring that for these types of trials, there's very close monitoring. So Petros, with the potential risk that we discussed, why would a patient participate? What are the benefits here?

Dr. Grivas: Brian, this is a critical question. And I think the purpose of cancer research and clinical trials is to try to benefit the patient individually, but also to try to move the field forward, in terms of more knowledge about cancer research, also benefit the community and the society, in general.

Dr. Shuch: How does a patient identify if a clinical trial's right for them? And how can they potentially participate?

Dr. Agarwal: I think the most important role is of the physician who is seeing the patient. And the physician may alert you to a specific clinical trial that is focused on your current condition. So maybe 10 or 15 or 20 clinical trials you saw on the Huntsman Cancer Institute website, but maybe 1 or 2 are specifically needed for a patient's given situation. Also, not every center has a clinical trial for every condition.

Dr. Shuch: We'll jump in to discuss 3 clinical trials that were chosen by members of Cancer.Net editorial board for genitourinary cancers. And they were basically chosen from the Trials in Progress abstracts that were submitted and presented at the ASCO GU 2020 Symposium. So because these are ongoing clinical trials, we may not have final results for these trials at this time. But I'd like to note that none of the members of this discussion have any direct involvement for these trials. For reference, all relevant disclosures can be found on the notes for this episode of Cancer.Net. So let's jump in. Neeraj, let's discuss the KEYLYNK-010 study. [Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010) (KEYLYNK-010)] Can you briefly summarize this study for us?

Dr. Agarwal: So this study is for patients who have progressive metastatic castrate-resistant prostate cancer, meaning the metastatic prostate cancer or advanced prostate cancer, which has already progressed on multiple previous lines of therapy, including chemotherapy and 1 of the novel hormonal therapies, which include enzalutamide and abiraterone. These are all standard therapies which are approved currently by FDA for treatment of our patients. Before I talk about this clinical trial, which includes multiple drugs, which is basically testing a combination of immunotherapy, pembrolizumab, with olaparib, which is a PARP inhibitor—and I'm going to explain those drugs in a moment—and comparing these drugs with other drugs, which are already approved by FDA and include enzalutamide and abiraterone. These drugs are manufactured by Merck, AstraZeneca, Pfizer, and Janssen. And I have consulted on a scientific advisory boards to all these companies and received honoraria for consulting to these companies.

So with that in the backdrop, I'd like to go ahead and briefly summarize this study. The patients who are progressing on the standard treatment option for metastatic castrate-resistant prostate cancer, including prior chemotherapy, and 1 of these novel hormonal therapies, which include abiraterone or enzalutamide, but not both, these patients are randomized on a 1-on-1 fashion to the novel combination of pembrolizumab with olaparib versus other hormonal therapy, which the patient has not received in the past. The patient's disease has progressed on abiraterone or enzalutamide. Then they are randomized to the novel combination pembrolizumab with olaparib versus abiraterone or enzalutamide.

Dr. Shuch: So Neeraj, what's the current standard of treatment for these patients at this time?

Dr. Agarwal: The current options are very limited. I would say the only chemotherapy, which may be used again, is docetaxel. Sometimes, we re-treat patients with 1 of these drugs on which they have already progressed. Cabazitaxel is another drug which can be used. But please note that by the time patients have already had disease progression on these previous therapies, the expected benefit by trying these currently available options are very limited. Most of the time, patients experience disease progression within 3 to 4 months on these currently-approved medications.

Dr. Shuch: So what is the exact problem that you're trying to solve or show with this study?

Dr. Agarwal: So pembrolizumab is an immunotherapy, and it's already approved for patients with multiple types of cancer. Olaparib is an oral pill which is already approved for patients with advanced breast cancer and ovarian cancer. Olaparib works by incapacitating the cancer cells from repairing their DNA, which in turns lead to cancer cell death.

Taking a step back, if when we treat patients with olaparib, these cells also get unusually sensitive to action by concomitant treatment with immunotherapy. And this is based on the laboratory data, pretty strong laboratory data. And hence, there is a rationale for combining pembrolizumab with olaparib. And what olaparib is doing is, it is killing the cancer cells by incapacitating them from repairing their DNA, and simultaneously making them very sensitive to action by immunotherapy. And then we are using pembrolizumab at the same time, which is immunotherapy, and hence we expect these 2 drugs to synergize, and lead to an exponential increase in cancer cell death.

Dr. Shuch: So Neeraj, so it sounds like there's pretty strong scientific rationale. But what question does this study aim to answer? Patients want to live longer? They want to be more stable on therapy?

Dr. Agarwal: The study has 2 major primary endpoints, which basically means 2 major questions the study is asking. Number 1 is, are patients going to live longer when they receive this novel combination versus standard therapy? And secondly, are they going to respond for [a] longer time, meaning they will have a longer duration of disease control defined as the radiographic progression-free survival. That is another primary endpoint of the study. So the study is asking whether patients are living longer, with better control of their disease with this novel combination.

Dr. Shuch: So Neeraj, with this new approach, are there any specific risks that patients would want to know about for this type of study?

Dr. Agarwal: Pembrolizumab is already FDA-approved for more than 10 different kinds of cancers at least. This is an immunotherapy, which basically up-regulates our immune system in a rather non-specific way. Most of the patients, the vast majority of patients take pembrolizumab very well with minimal side effects. But then a small minority of patients, I would say somewhere around 4 to 5 percent, patients have hyper activation of the immune system, which can attack our own organs. So the most common side effects with any immune checkpoint inhibitor like pembrolizumab include diarrhea, liver toxicity, skin toxicity, and less frequently lung toxicity, or attack of immune system on the endocrine glands. These are only some of the toxicities which we usually see on our clinic, but it doesn't mean other rare toxicities may not happen. So these drugs require close monitoring. They're given every 3 weeks. So pembrolizumab, especially, is given every 3 weeks. And it is very important that patients are seen regularly by their oncology providers, so that if there are any of these toxicities are happening, they can be controlled at a much earlier stage, rather than becoming very severe and being picked up at a more severe stage.

So I just want to add the toxicities of olaparib, which is already approved for patients with breast cancer and ovarian cancer. So we are not talking about any experimental drugs here for human beings. Both of these drugs are approved for various cancers already, with very well-defined toxicity profile. The combination is unique. Combination is being tested for the first time. So olaparib can cause bone marrow suppression, which basically means it can lead to anemia, low platelet counts, and low neutrophils, which are the defense cells fighting for us against infection. Most of these toxicities are easily manageable by modifying the dose of olaparib.

Dr. Shuch: Neeraj, it sounds like this could be a really important study, and we'll keep an eye out for future updates. Please keep us posted. So let's move on to some of the exciting kind of work in bladder cancer. Petros, can you discuss this ongoing study that was presented at ASCO GU, the KEYNOTE-866 protocol? [Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866) (KEYNOTE-866)]

Dr. Grivas: Sure. Before I start, I want to say that I have done consulting with this trial sponsor, which happens to be Merck, for unrelated reasons and not for this trial. And this trial is open in our institution, but I'm not involved directly into that study. This particular clinical trial is trying to evaluate the following question. Right now, the standard of care for patients who are aiming to go for removal of the bladder—we call this radical cystectomy—is to get chemotherapy with the regimen consisting of gemcitabine and cisplatin combination chemotherapy before cystectomy. We call this pre-operative, before the operation, or neoadjuvant cisplatin-based chemotherapy. And that's a standard of care in patients who are fit enough to tolerate this study, because this study can cause side effects. So the question is, can you now use immunotherapy, in particularly this drug called pembrolizumab, which is activating the immune system, in combination with chemotherapy. So chemotherapy plus, pembrolizumab, as compared to chemotherapy plus placebo before patients get cystectomy, removal of the bladder.

Dr. Shuch: So these are patients who are going to go for surgery?

Dr. Grivas: That is correct. This patient population are those patients who have made a decision to go for removal of the bladder, and we call this, as I mentioned, radical cystectomy. And I mention this because there are some other treatment approaches.

Dr. Shuch: The current standard of care is chemotherapy and then surgery. So what is the problem that the researchers are trying to solve?

Dr. Grivas: The main question is, does the addition of this immunotherapy to chemotherapy increases chance and [the likelihood of] not finding any residual cancer when the bladder is removed, and whether it actually increased the time of being cancer-free and alive down the road. So does the addition of immunotherapy to chemotherapy improves how these patients do over time, in terms of less of cancer recurrence, meaning cancer coming back, and longer life?

Dr. Shuch: Okay. So you want to see the tumors disappear, and then you want to prevent patients from having recurrences with this study.

Dr. Grivas: That is correct, and ideally, live longer, if possible.

Dr. Shuch: And how was it specifically designed? What was the rationale with this type of approach?

Dr. Grivas: Brian, this is an important question because we have to use previous information to inform the design of those trials. And I would mention that there are some observations about chemotherapy and immunotherapy combinations might work well in other cancer types. And particularly, in patients with bladder cancer, there were a few previews, smaller-sized clinical trials that showed promising results, meaning higher chance of making the cancer disappear when they take the bladder out. And because those trials were very promising and also showed that the combination of chemotherapy and immunotherapy was feasible, then the bigger trials now being launched to confirm the results and compare this combination with the standard of care right now. So strong previous data supports this larger trial to evaluate whether this addition makes sense.

Dr. Shuch: So, Petros, patients generally are going to go to surgery. You're giving them a different medication, immune medication. What would be additional risk that patients would have with this approach?

Dr. Grivas: So every time you add a new therapy, there is a chance of side effects as Dr. Agarwal mentioned before. And particularly, when you add immunotherapy, there is a small but real chance of having immunotherapy-related adverse events. And that's what we call side effects from a very activated active immune system. And I think it's important to have this discussion with the patient about benefits or risks before the trial starts. And before the patient makes a decision. Overall, these immunotherapy-related adverse events usually, as I mentioned, are not very common, especially when we compare the immunotherapy with the chemotherapy. However, we have to be very careful, especially with a combination. And these patients are monitored very closely for any side effect that might happen. And I think education is important for both the patient and the medical provider team, how to monitor and do a close observation for those side effects. The side effects of chemotherapy are standard. And that is something that's also a part of the discussion with the patient.

Dr. Shuch: Got it. And is this still open? And when do you think we'll see results for this work?

Dr. Grivas: Yes. The trial is still open. There is a way to go. It started accrual fairly recently, and I think their efforts for accruing patients in multiple cancer centers. So I would definitely consider this clinical trial for patients who are thinking about getting removal of the bladder and who [are well enough to] get chemotherapy, and they can discuss that option with a medical provider because the trial's going to be open at their cancer center or another cancer center. So definitely, it's open and accruing patients.

Dr. Shuch: I see. It seems very exciting that they're moving this type of therapy to a new space. Petros, keep us posted as this trial progresses.

Dr. Grivas: Thank you. Will do.

Dr. Shuch: So moving on to kidney cancer. Monty, let's discuss this PDIGREE trial. [Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study] Besides obviously having a very interesting name, it seems like it's a pretty novel type of approach. Can you briefly summarize the study and design?

Dr. Pal: Yeah. Thanks, Brian. So the intent of this study is to take patients with advanced kidney cancer—these are folks where the cancer has [spread] beyond the borders of the kidney to the lungs, to the liver etc. All patients receive standard immune-based treatment in the upfront setting. And then a couple of months in, they actually look at the response that they've achieved, and based on that, decide on different lines of treatment beyond that.

Dr. Shuch: So who is the ideal patient for this study? Who is it intended for?

Dr. Pal: Yes. So this particular study, as I've mentioned, is really for those patients with advanced disease. And beyond that, we in the clinic are using different criteria [to assess] how functional a patient is. It's based on their labs, etc., to define whether or not they have what's termed good risk, intermediate risk, or poor risk. And I think as you're looking at treatment options, as a patient with kidney cancer, it's important to figure out which one of those risk criteria you fit into. This particular trial is intended for patients with intermediate and poor risk.

Dr. Shuch: Got it. So these are patients that are newly diagnosed. Correct?

Dr. Pal: Exactly. Exactly.

Dr. Shuch: So what is the current standard of care for these patients? What would you give them outside of this trial?

Dr. Pal: There's a number of options for kidney cancer. When I started in this business, we only had about 2 to 3 treatments for the disease. And now, it's expanded to more than 12 FDA-approved therapies, which is just mind-boggling. Typically, if you're just diagnosed with advanced or metastatic kidney cancer, you'll start with a combination of immune treatments, 2 immune therapies. And that's really the basis of this particular trial. Or you might get a mix of targeted treatment and immune treatment up front.

Dr. Shuch: So Monty, if we have so many exciting therapies, what is the problem that the clinical trial team is trying to solve here?

Dr. Pal: Great question. I think the big issue is that we know that patients who aren't doing well in therapy need to be switched. We know that patients who are doing exceptionally well on therapy can be continued on their current treatment. For the in-betweens, for patients who might have some stability in their tumors, but maybe not the type of shrinkage that we want to see, we really don't know what the best option is. And that's really where the PDIGREE trial comes into play.

Dr. Shuch: So with that in mind, how is it designed to kind of answer that question?

Dr. Pal: So again, we're taking patients who are receiving immune therapy in the upfront setting. We're taking a look at their response at around the 3-month mark. And typically, if you're a patient with kidney cancer, that's how often I would image you with scans. So at the 3-month mark, we look and see. If you've got a complete response—I think it's pretty intuitive—you're just going to continue on immune treatment. If you're actually having a very poor response, meaning the cancer is continuing to grow, it's migrating to new sites, you'll go on to targeted therapy.

On the other hand, if you're in-between, if tumors are maybe shrinking more modestly, or just staying the same size for the most part, that's when you would be randomized to either continue on immune therapy alone, or go on a mix of targeted therapy with immune therapy.

Dr. Shuch: So what is the overall question that the study is hoping to answer? The patients who are getting that additional targeted therapy, what is the hope for them?

Dr. Pal: I think really what we're hoping to see is that those patients actually have delays in their cancer progression. There will be a longer time until they see their cancer grow. Furthermore, we're hoping, actually, that we might improve the survival of these patients.

Dr. Shuch: Got it. So the patients who are starting this therapy, and they have an additional medication, that targeted drug, what would their specific risk be by participating in this study with that drugs?

Dr. Pal: So we've had some great conversations with Dr. Agarwal around the targeted therapy in prostate cancer. He was talking about PARP inhibitors. In kidney cancer, the general principle of targeted therapies are they tend to cut off the blood supply to tumors. But they don't just do it there. They can do it in other organ systems, as well. By virtue of that, you can have a handful of different side effects, including hand-foot syndrome, which is peeling of the skin on the hands and soles of the feet. You can potentially have high blood pressure as a consequence of that mechanism. You can also have diarrhea. These tend to impact the gut. Those tend to be some of the principal side effects. But, of course, I always refer patients to the consent form for these studies for a more exhaustive review.

Dr. Shuch: Got it. But some patients may not have any of these side effects. True?

Dr. Pal: You're absolutely right. It's just amazing to me that I have more than a handful of patients in my practice who experience little or none of these toxicities. Having said that, it's still so important to disclose the possibilities when you're discussing these trials.

Dr. Shuch: Got it. Is this trial still open to patients? And when do you think the results would be available?

Dr. Pal: So at this particular trial is planning to accrue several hundred patients. And we're really in the trial's infancy. We've just had over about 150 patients accrued to date. So there's still ample opportunity to get the study for your patients in practice. And to the patients who are listening to this, it's certainly a trial that I would like you to inquire about at your respective cancer centers. It's open all over the country.

Dr. Shuch: Well, Monty, that seems really fascinating. The idea that it's an adaptable trial, that patients start on therapy, and you see how they do. We'll definitely keep an eye out for that trial in the next few years.

Dr. Pal: Thanks a lot, Brian.

Dr. Shuch: Great. So thanks to our guests. Thank you for tuning into this podcast. I'd like to thank my guests Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta Pal. There are many types of clinical trials for urologic cancers that are ongoing, all with the shared goal of improving the way we treat these diseases. If you're wondering about participating in a clinical trial that might be right for you, definitely, talk to your healthcare provider. Please tune in next time for further discussions on additional advances in our urologic cancer field. Thank you so much.

ASCO: Thank you, Drs. Shuch, Agarwal, Grivas, and Pal.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

ASCO: Usted está escuchando un pódcast de Cancer.Net en español. Este sitio web de información sobre el cáncer es producido por la Sociedad Estadounidense de Oncología Clínica, o la American Society of Clinical Oncology en inglés, la organización profesional líder en el mundo para médicos que atienden a personas con cáncer.

El propósito de este pódcast es instruir y brindar información. Esto no es un sustituto de la atención médica profesional y no está previsto que sea utilizado para el diagnóstico o el tratamiento de afecciones individuales. Los invitados de este pódcast expresan sus opiniones, experiencias y conclusiones. La mención de cualquier producto, servicio, organización, actividad o terapia no debe considerarse como aval por parte de la American Society of Clinical Oncology. La investigación sobre el cáncer que se analiza en este pódcast está en curso; por lo tanto, los datos descritos aquí pueden variar a medida que la investigación avanza.

Leslie Zhang: Bienvenidos al podcast de Cancer.Net. Soy Leslie Zhang, una escritora en el equipo de Cancer.Net. Como recordatorio, Cancer.Net es un sitio web de información para los pacientes por ASCO, la Sociedad Estadounidense de Oncología Clínica. Pueden encontrar más episodios del podcast Cancer.Net en nuestro sitio Cancer.Net/blog/podcast. Hoy hablamos sobre la evaluación geriátrica integral y su utilidad en el cuidado de las personas con cáncer. Nuestro invitado hoy es el doctor Enrique Soto, un oncólogo clínico que se especializa en el cuidado de los adultos mayores con cáncer. El doctor Soto trabaja en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán en la Ciudad de México. Es un miembro nuevo de la junta directiva de ASCO y miembro de la junta editorial de Cancer.Net. Bienvenidos al podcast de Cancer.Net, doctor Soto.

Dr. Enrique Soto: Hola, ¿qué tal Leslie? Muchas gracias por invitarme a este podcast, es un verdadero placer estar aquí.

Leslie Zhang: Gracias. Voy a empezar con las preguntas. Primero, ¿qué es una evaluación geriátrica integral? ¿Que necesitan saber los pacientes sobre la evaluación geriátrica integral?

Dr. Enrique Soto: La evaluación geriátrica integral es una herramienta que utilizan los geriatras, que son los médicos que se encargan de atender a los pacientes adultos mayores, para evaluar a los pacientes de una forma multidisciplinaria, que permita conocer todas las cosas que están sucediendo con esa persona. O sea, es como una consulta médica usual, pero tiene el extra de que se evalúan cosas que son particularmente importantes en las personas mayores. Y la idea es que a través de esta consulta, se logre una visión general integral de las capacidades funcionales, el rendimiento físico, el estado nutricional, las diferentes enfermedades que tienen las personas, la capacidad cognitiva, o sea, la memoria y la capacidad para pensar, el estado psicológico, estado de ánimo y las condiciones de apoyo social y financieras de las personas mayores. Entonces, a través de una serie de preguntas, de cuestionarios y de herramientas que ya están diseñadas desde antes, se evalúan todas estas características de las personas mayores y con eso se logra un entendimiento holístico de la persona en el que todos los aspectos se consideran, y esta evaluación permite encontrar cosas que no se encuentran normalmente en la consulta normal de un oncólogo, en la que se ven algunas cosas y aquí se ven cosas adicionales.

Leslie Zhang: Perfecto. ¿Por qué es importante una evaluación geriátrica para un oncólogo para su tratamiento del cáncer de los pacientes?

Dr. Enrique Soto: Normalmente, las valoraciones oncológicas incluyen valoraciones de la capacidad funcional de las personas, pero suelen ser cosas muy sencillas y unidimensionales. Y eso no necesariamente es lo mejor para las personas mayores, conforme la gente va envejeciendo todos nos volvemos muy diferentes entre nosotros. Y, después de cierta edad el número de años que tiene la gente nos dice muy poco sobre quién es realmente esa persona y qué cosas realmente están sucediendo en su vida. Entonces todos conocemos personas mayores, mayores de 70, mayores de 80, que son extremadamente activas, que son muy independientes, que hacen muchísimas cosas en su vida diaria, y a lo mejor conocemos personas más jóvenes que necesitan ayuda de los demás, que no pueden valerse por sí mismos. Y esto es mucho más importante que el número de años que tiene la gente, y la forma de detectar estas cosas que pueden hacer las personas, es a través de la valoración geriátrica. Entonces, la valoración geriátrica nos da una idea de la verdadera edad biológica de las personas. Y en oncología en particular, nos puede ayudar a predecir la expectativa de vida de los pacientes, a ver qué tanto riesgo tienen de tener toxicidad por los tratamientos, particularmente por la quimioterapia. Y una cosa extremadamente importante es que nos permite encontrar otras cosas que pueden andar mal y en las que al hacer intervenciones, podemos mejorar el estado general de las personas. Si a través de la valoración geriátrica encontramos que las personas están mal de ánimo, que tienen problemas para caminar, que necesitan ayuda social, podemos intervenir en esas cosas y mejorar la calidad de vida global de los pacientes.

Leslie Zhang: Perfecto. ¿Y cómo afectan el tratamiento de un paciente los resultados de una evaluación geriátrica?

Dr. Enrique Soto: Hay muchas formas en las que los resultados de la valoración geriátrica y la intervención de un oncólogo geriatra o de un geriatra, pueden modificar o afectar los tratamientos. Entonces, la evaluación lo que nos puede ayudar es a descubrir vulnerabilidades adicionales que no se detectan normalmente en la historia clínica. Y eso puede hacer que nosotros, durante y después del tratamiento, hagamos intervenciones que estén encaminadas a mejorar estos problemas. Por ejemplo, otra cosa para la que sirve muy bien o para la que se utiliza mucho la valoración geriátrica es para predecir qué tanto las otras enfermedades de los pacientes afectan el tratamiento del cáncer al calcular la expectativa de vida de la gente, y eso nos puede ayudar a tomar decisiones difíciles con los pacientes. A veces, nuestros tratamientos tienen riesgos que pueden superar los riesgos de las enfermedades. Entonces, eso nos ayuda a poner las cosas en la balanza. Y también, y esto es un área de estudio en oncología geriátrica, podemos utilizar la valoración geriátrica para identificar a aquellos pacientes más vulnerables, que tienen más riesgo de tener complicaciones en los tratamientos, y en los cuales hacer algún ajuste en los medicamentos, que puede ser reducir la dosis, cambiar el tipo de medicamentos que utilizamos, puedan hacer que los tratamientos se toleren mejor y se completen de mejor forma. Y hay otras cosas más, por ejemplo, si encontramos que los pacientes tienen problemas de la memoria o problemas cognitivos, podemos ayudarlos mejor a tomar decisiones, apoyándonos además en su familia. Todo este tipo de cosas nos ayudan a que la toma de decisiones compartidas entre los pacientes y los médicos sea más efectiva y que podamos hacer tratamientos que resuelvan el problema de los pacientes causando el menor daño posible.

Leslie Zhang: Sí. ¿Y tiene usted ejemplos de otras enfermedades que pueden afectar el tratamiento del cáncer?

Dr. Enrique Soto: Claro. Una enfermedad muy importante que puede afectar el tratamiento del cáncer, y que es muy común en las personas mayores, son los problemas cognitivos, la demencia. Entonces, con el paso del tiempo, muchos pacientes mayores desarrollan problemas de memoria y problemas de la atención y de la capacidad de toma de decisiones. Y de hecho eso es una cosa para la que mandan muy comúnmente a los pacientes mayores a las consultas de geriatría o de oncología geriátrica. A través de la valoración geriátrica se puede determinar qué pacientes tienen limitaciones para la toma de decisiones, y en esos casos determinar qué tanto ofrecer tratamientos potencialmente tóxicos, es una cosa que le haría más daño que beneficio al paciente. Entonces, esto es una cosa extremadamente importante que hace la oncología geriátrica, detectar los problemas cognitivos. Otra cosa muy común que normalmente no se toma en cuenta en las consultas de oncología es la presencia de caídas. Las personas mayores con cáncer tienen más riesgo de caerse, y al caerse pueden, por ejemplo, fracturarse la cadera, y esto tiene consecuencias muy importantes, tanto para la supervivencia como para la calidad de vida. Entonces detectar de forma temprana que los pacientes tienen riesgo de caídas puede hacer que evitemos algunos medicamentos que aumentan ese riesgo y también que implementemos intervenciones para evitar que las personas se caigan, como por ejemplo, darles un bastón o adecuar su casa para que sea más segura o enviarlos a terapia física o a terapia ocupacional para que ese riesgo disminuya.

Leslie Zhang: ¿Y hay otras cosas que las personas mayores con cáncer puedan hacer para adecuar su casa?

Dr. Enrique Soto: Bueno, en los Estados Unidos, particularmente, existen algunos servicios que ayudan a que las personas mayores adecuen su casa. En otros lugares del mundo esto no es tan común, pero sí evitar que existan obstáculos en la casa, en algunos casos los pacientes tienen mucho riesgo de caídas; evitar que los pacientes tengan que subir y bajar escaleras para llegar a su cuarto; utilizar auxiliares de la marcha, como por ejemplo, bastones o andaderas. Es importante que las prescriba un rehabilitador que seleccione el auxiliar de la marcha apropiado para cada paciente. Y también, mejorar la nutrición y mejorar la fuerza física, todo eso puede disminuir el riesgo de caídas. Y para esto, existen en la mayoría de los centros de cáncer, equipos multidisciplinarios que pueden ayudar a esto. Prácticamente todos los centros de cáncer en los Estados Unidos tienen equipos de fisioterapia o de terapia ocupacional que pueden ayudar mucho para que esto no pase.

Leslie Zhang: ¿Y es posible que los pacientes les pidan que sus oncólogos le hicieran una evaluación geriátrica si no es parte de la evaluación estándar?

Dr. Enrique Soto: Bueno, yo no diría que la valoración geriátrica no es parte de la valoración estándar. Yo creo que hoy en día en todos los pacientes adultos mayores, se debe de hacer una valoración geriátrica antes de empezar el tratamiento para el cáncer. De hecho, desde el año pasado la Sociedad Americana de Oncología, ASCO, publicó las guías para el cuidado de los adultos mayores con cáncer. Y parte de las recomendaciones es que en todas las personas mayores, antes de empezar un nuevo tratamiento para cáncer, se haga una valoración geriátrica y se revisen ciertas cosas específicas: La función física, la memoria, el estado de ánimo, el estado nutricional. Entonces en realidad esto es algo que todos los oncólogos deberíamos de tener en cuenta, que en las personas mayores necesitamos ir un poco más profundo y evaluar estos aspectos a través de la valoración geriátrica. Y además, es algo que se puede hacer en una consulta normal. Hay varias demostraciones de que esto se puede hacer en un lapso de tiempo no muy largo, y que nos da un montón de información que es muy útil para las personas mayores. Entonces yo creo que sí. Los pacientes mayores deben pedirle a sus oncólogos que los vea un geriatra o un equipo geriátrico si es que este está disponible, por supuesto, en el centro donde están los pacientes.

Leslie Zhang: Parece que las valoraciones geriátricas integrales son una herramienta importante para los oncólogos y son esenciales para determinar el mejor curso de tratamiento con menos efectos secundarios adversos. Gracias por su tiempo hoy, doctor Soto.

Dr. Enrique Soto: Muchísimas gracias Leslie por invitarme y espero que esto haya sido de utilidad para los pacientes y para sus cuidadores. Muchas gracias.

ASCO: Encuentre más información de confianza para personas con cáncer en www.cancer.net/es. Y si este pódcast fue útil, tómese un minuto para suscribirse, dar una calificación y escribir una reseña del programa en Apple Podcasts o Google Play.

Cancer.Net está respaldado por Conquer Cancer, la fundación de la American Society of Clinical Oncology que financia la investigación de vanguardia sobre todos los tipos de cáncer para ayudar a pacientes de todo el mundo. Para ayudar con la financiación de Cancer.Net y programas similares, haga su donación en conquer.org/support.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Tian Zhang.

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Novartis, Genentech Roche, and Bristol-Myers Squibb.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Novartis and Bristol-Myers Squibb.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for Genentech Roche and Bristol-Myers Squibb.

Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Genentech Roche and Bristol-Myers Squibb.

View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Grivas, and Dr. Zhang at Cancer.Net.

Dr. Pal: Hi, I'm Monty Pal from City of Hope. I'm the Associate Editor for Genitourinary Cancers for Cancer.Net, ASCO's patient education website. I'm really excited to be here with my colleagues: Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang. We're really excited about this effort. We're hoping it brings some salient details about clinical trials straight to you, our most important audience. Keep in mind that clinical trials are the main way that doctors are able to find better treatments for diseases like cancer. And before any new drug can be approved by the FDA, it must be studied in the context of a clinical trial. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatments, reduce side effects, or even reduce the risk of cancer altogether. While you may receive new treatments within a clinical trial, the primary purpose of these studies is to move the field of cancer research forward. Keeping participants safe is probably the most important concern in clinical trials, and there may be some risks involved. Because of that, your healthcare team is going to discuss with you in detail these risks before you join on to a clinical study.

Now, at this point in time, we're going to discuss 3 studies that are being done in the area of kidney, bladder, and prostate cancer. These studies were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that are going to be presented at ASCO's 2020 Genitourinary Cancers Symposium. I'd like to note that none of us have any direct involvement with any of these trials. Each one of us will post our disclosures on the ASCO website if you'd like to see them. We'll certainly have them posted on the Cancer.Net website.

I'd like to begin by introducing my very esteemed panel. First, is Dr. Tian Zhang, who's an expert in kidney, bladder, and prostate cancer from Duke Cancer Research Institute. We have Dr. Neeraj Agarwal, who heads up the Genitourinary Cancers Program at the Huntsman Cancer Institute at the University of Utah. And last, but not least, we have Dr. Petros Grivas from the Fred Hutchinson Cancer Research Institute in Seattle, Washington, an expert in many disease types, including bladder cancer.

I'd like to bring on my first guest, Dr. Neeraj Agarwal, to discuss the VISION study. [VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)] Neeraj, this is a study in prostate cancer. What particular patient population within prostate cancer are we focused on here with this study?

Dr. Agarwal: So this is a patient population with advanced prostate cancer where prostate cancer has gone beyond prostate to different parts of the body. In technical terms, we call it metastatic prostate cancer. The usual treatment paradigm for these patients is to be treated with hormonal blockade therapies, which can include injections and oral pills, which have different mechanisms to prevent stimulation of testosterone to the prostate cancer cells. However, every patient with metastatic prostate cancer eventually are failed by these treatment options, and the next commonly used treatment option is chemotherapy, which usually controls the disease for a period of many months, up to one year. And after, patient's disease progresses on these 2 different therapeutic options, which include hormonal therapies and chemotherapies. And this is the patient population in which this novel type of radiation therapy or radiation particle treatment is being tested.

Dr. Pal: Tell us about what question this study aims to answer.

Dr. Agarwal: This study is testing a novel medication, which is a type of a radiation particle, which is supposed to target prostate cancer cells. So whether using this kind of radiation particle in patients with advanced prostate cancer, who have been failed by previous chemotherapy and novel, hormonal therapies. The study is asking whether using this radiation particle as a treatment may improve overall survival.

Dr. Pal: Now, this compound is called 177Lutetium-PSMA-617. It's a long name. Tell us about what it actually does. What's the rationale for using this particular drug?

Dr. Agarwal: I would like to divide this long name into 2 parts to make it simple. So 1 is the lutetium particle, which is the radiation particle, is a type of radiation known as beta radiation. So lutetium is tagged onto a PSMA-identifying agent known as PSMA-617. So if we just inject PSMA-617, it will go and seek prostate cancer cells, which are expressing PSMA on their surface. If you tag this radiation particle lutetium to the PSMA-617, what essentially happens is that PSMA-617 takes this radiation particle directly to the prostate cancer cells.

Dr. Pal: Now, what is this study attempting to demonstrate?

Dr. Agarwal: This study is specifically looking at 1 question, which is whether using this radiation particle can improve survival in patients with metastatic prostate cancer who have had disease progression on novel hormonal therapies and chemotherapies.

Dr. Pal: And again, it's hard to be comprehensive in a podcast like this, so of course, we refer patients to their physicians for a discussion around safety of these drugs. But could you tell us about any known risks that patients should be aware of in the context of this agent?

Dr. Agarwal: Yes. So as you can imagine, this PSMA-617, which is loaded with this radiation particle, is looking for those cells in our body which are expressing PSMA. So of course, the PSMA is expressed highly by prostate cancer cells. But there are also normal cells which express PSMA to a lesser degree. And those cells may also have the potential to be targeted by this radiation particle. So technically, their other cells which may express PSMA, or which are in the vicinity of these cancer cells in the bone, such as bone marrow, these can be targeted to a much lesser degree because of the specificity of this compound. We can see some off-target toxicities, as we call them, but given the highly targeted nature of this compound, those toxicities are usually very well tolerated, except in rare circumstances.

Dr. Pal: Excellent, Neeraj. Now, for a little additional commentary on the VISION trial, I'm going to throw it to Dr. Tian Zhang, again, an expert at the Duke Cancer Research Institute Tian, you've had some experience enrolling patients on VISION, correct?

Dr. Zhang: That's right, Monty. Thanks so much for having me on. And VISION has actually completed accrual. It was open for a few months here at Duke. We were able to enroll about 10 patients and we're really looking forward to seeing the results of VISION over the next year or 2. And I think it'll be quite applicable to clinical practice. Now, I want to mention that although VISION has completed enrollment, there are other clinical trials that are using PSMA-targeted Lutetium-617 agent as a possibility for other patients to enroll on to other trials in clinical development as we speak, and so there will be other opportunities to receive this agent.

Dr. Pal: We're going to shift gears now from prostate cancer and move on to the topic of bladder cancer. And again, I'm thrilled to have Dr. Petros Grivas from the Fred Hutch Cancer Research Institute to discuss a very important trial called INTACT. [Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)] Petros, the study INTACT really addresses a very important question. Can you tell us a little bit more about it?

Dr. Grivas: Thank you, Monty. I think this trial is very important for a number of reasons.

Number 1 is trying to address an important clinical question, which is the following:

Patients who we consider candidates for bladder-preservation approach, meaning, we try to keep the bladder in place and still kill the cancer, which is not a good option for everybody with bladder cancer. But the proportion of patients after discussions of pros and cons with their providers could be offered this bladder-preservation approach, which is consisted of an optimal resection of the tumor through a procedure called transrectal bladder tumor resection, which means try to remove the bladder tumor through a procedure that is similar to cystoscopy, when you look inside the bladder. And after this tumor is removed, then there is a combination of chemotherapy and radiation, at the same time—we call this concurrent or concomitant—at the same time, chemotherapy and radiation. This approach, which involves the collaboration between the urologic oncologist, medical oncologist, and radiation oncologist, is the standard of care, the standard approach, how we try to preserve the bladder and still kill the cancer in those patients who are considered good candidates for this approach, which, as I've mentioned, is not for everybody.

The clinical question is can we improve upon this backbone of chemotherapy and radiation, which is current standard of care, by using a third modality, a third type of treatment, which is immunotherapy? And immunotherapy is known to improve how people live in patients who have metastatic bladder cancer. For example, there's this particular drug called atezolizumab, which is already having FDA approval for patients with metastatic bladder cancer. The question is can we add this drug, the immunotherapy drug, that is activating the immune system, into the backbone of chemotherapy and radiation and use all three approaches, chemotherapy, radiation and immunotherapy together? And if that's the case, is that triplet combination better or not to the current standard of care, which is chemotherapy and radiation?

So the INTACT trial is chemotherapy, radiation, plus immunotherapy with this drug called atezolizumab, together, all 3 of them compared to chemotherapy and radiation alone, in order to see whether we can improve upon the results we're getting with chemotherapy and radiation. The primary end point of this particular trial is what we call bladder intact disease-free survival, which means the proportion of patients who have no cancer coming back after treatment. They have what we call a complete response, remission of the cancer, and they still have the bladder intact, in place. And this is what we call a metric of success. This is a huge effort among different investigators across the country. These studies open in multiple cancer centers and sites across the nation. And I think it's a very good example of what can happen in terms of a clinical trial design that is applicable to many patients when different collaborations take place and when people put their minds together. So we're really very enthusiastic about this study, and we'll try to support the accrual and offer this option to the patients who are considered to be good candidates for this attempt for bladder preservation.

Dr. Pal: Petros, thanks. That was a great overview of the study. You've really highlighted the rationale and some detail and the metrics for success of this trial. Now, on the subject of this approach, are there any risks that you think patients should be particularly aware of? And again, we leave it to the discretion of treating physicians to have that very thorough discussion of risks and benefits. But off the top of your head what would you counsel patients, in general?

Dr. Grivas: I think, Monty, that's a great question, in general, because when a patient is undergoing evaluation for a clinical trial, it's important for them to understand thoroughly the pros and cons of this particular therapy and other procedures and what those mean for the patient's logistical, day-to-day schedules, as well as potential short-term and long-term side effects. In that particular study, I think the important take-home message is we're trying to evaluate the additional role of immunotherapy to the backbone of chemotherapy and radiation. So potential side effects of immunotherapy are something that are very important to be discussed with the patient. Some of the patients may develop fatigue or some degree of occurrence of what we call immune-related adverse events, which means the immune system gets activated, stimulated against the cancer but can, potentially, in a small proportion of patients generate a significant reaction, an immune system activated related reaction against different parts of the body or some parts of the body.

So I think it's very important for the patients to discuss carefully with the providers what are those uncommon, but sometimes significant, immune-related adverse events, and have a very good understanding of what symptoms [to] look for in order to be able to communicate or recognize early those potential side effects and have a proper management plan. Because most of those side effects could be managed properly, and with good success, especially if they're caught up early. So I think it's important to have these thorough discussions with the provider. And of course, the side effects of chemotherapy and radiation should be discussed in thorough detail. This is the standard of care, but still is important to delineate what potential side effects can happen. At the end of the day, it's in the balanced discussion about pros and cons. This is a very exciting trial, but I think good education for the patient and their families and their caregivers are very important and critical for the successful detection or diagnosis of any potential side effects. Overall, I think this is a very relevant discussion to have with the provider and a very exciting trial to be involved in.

Dr. Pal: Excellent, Petros. Well, great discussion of some of the risks associated with this approach. Neeraj, any thoughts on INTACT? Why should patients be excited about this particular trial?

Dr. Agarwal: I was recently talking to one of my patients about this upcoming trial, who is preparing to go on radiation therapy plus chemotherapy as a treatment option for his muscle-invasive bladder cancer, and cystectomy is not an option. And the way I explained this to the patient is 95% of the work he will have to do will be done by the time he's getting radiation therapy and chemotherapy. And after that, 5% of the work, as far as patient's effort, side effects, toxicities, impact, and quality of life, all are concerns, 95% of that, in my view, is coming from radiation therapy and chemotherapy. And after that, little work from that perspective by the patient has to be done by atezolizumab, as far as getting treatment with atezolizumab is concerned. So as Petros said, this is a highly well-tolerated treatment, which is immunotherapy. And if you look at the potential of this drug to control the recurrence of the disease and allow our patients to maintain their bladder—it's tremendous. So I think the expected returns are very high, and how much effort patients will have to put on the trials are not as high as you would expect if you are thinking about a trial.

Dr. Pal: That was an excellent discussion of toxicities associated with this particular regimen, Neeraj. Petros, before we move on any closing thoughts?

Dr. Grivas: No, I agree completely with Neeraj. I think these are important points. I just wanted to add a couple of key take-home message for the patients. Number 1, this trial is available for patients who either are or are not candidates for radical cystectomy, which is the removal of the bladder and again, it has to be a discussion with the providers whether they're good candidates for the attempt for bladder preservation. Half of the patients get the standard of care, which is chemotherapy and radiation at the same time, and the other half get chemotherapy and radiation, plus this immunotherapy called atezolizumab. And again, I think the last point to make is that chemotherapy and radiation have to happen at the cancer center, and some of the patients live far away, so I think it's important to discuss with the patients the pros and cons of the trial because it might entail some back and forth transportation for them if they have to get the radiation and the chemotherapy in the cancer center that is offering the trial. But overall, as Neeraj pointed out, we are very enthusiastic, and I'm personally enthusiastic about the study.

Dr. Pal: That's great Petros, appreciate that. Now, in the final portion of our program, we're going to shift gears and talk about the type of cancer that I actually focus on personally in the clinic, and that is kidney cancer. And we have our resident expert in kidney cancer on the Cancer.Net panel, Dr. Tian Zhang from Duke here to discuss the PROSPER study, a very important national effort. [A Phase 3 Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)] Tian, can you tell us about PROSPER?

Dr. Zhang: PROSPER is a phase III trial that's open currently for patients who have locally advanced kidney cancer, and we know that in this population of patients who have locally advanced kidney cancer who undergo their surgery, there's still a high rate of recurrence up to about 50% with many dying, unfortunately, from disease recurrence.

And so the question that PROSPER aims to answer is can we prevent disease from recurring, and thereby, can we allow patients to live longer from giving up-front systemic therapy in addition to their surgery? And so in kidney cancer, we know that patients will benefit from immune checkpoint inhibitors, and the big question of the study is that with the primary kidney cancer in place, what is the effect of this immunotherapy called nivolumab before and after surgery compared to surgery alone, and how should we use these immunotherapy agents in the perioperative setting to improve overall survival?

Dr. Pal: That's very interesting. Of course, in kidney cancer, just as we discussed with prostate cancer, you've got patients who have the disease confined to the kidney. You have patients where the disease has spread. What particular patient population does this study focus on?

Dr. Zhang: This study is enrolling patients with locally advanced disease, so either clinical stage II or higher. So that's patients who have primary tumors of greater than seven centimeters, or if they have positive lymph nodes on their scan, so clinical detection of lymph node-positive cancer. Or the study, actually, also allows cancer that has spread to no more than three, so one, two, or three, other sites, which can also be definitively treated at the time of the primary surgery. Patients who have disease spread to the lung, adrenal gland, lymph nodes, pancreas, or soft tissue are allowed. Patients who have spread to the liver or bone are not allowed. And the study is currently ongoing, Monty. It is randomizing up to 805 patients total. As of late January 2020, they're currently at about 390 patients already enrolled. So there's plenty more, about 400 more patients to go on the study. And it is an open and enrolling study.

Dr. Pal: That's really interesting. Now, Petros gave us some insights as to the rationale for using immunotherapy in cancer. Is it the same rationale for using this treatment strategy in kidney cancer?

Dr. Zhang: Sure. So our standard of care in this setting, as you know, for locally advanced disease is truly just nephrectomy alone to remove the kidney, usually without treatment afterward. And there are multiple adjuvant studies using immunotherapies in this post-operative setting, however, those are all pending. And we're hoping that immunotherapy used earlier in the disease course will allow us to see a benefit overall. Now, nivolumab, the immunotherapy that's studied in the PROSPER trial, is approved for metastatic kidney cancer. And therefore, we know nivolumab is effective at extending overall survival for these patients. And so the question is if we can use this active immunotherapy agent earlier in the disease course if we can to try to prevent disease recurrence.

Dr. Pal: That makes a lot of sense. Now, what is this particular study attempting to demonstrate? What are we trying to prove here with this trial?

Dr. Zhang: Right. So the primary outcome of PROSPER is the time to disease recurrence or spread to other sites, what we call recurrence free-survival. There are secondary outcomes. So trying to get patients to live longer, overall survival, toxicity of giving nivolumab up front for these patients. As well as, specifically in patients who have clear cell kidney cancer, the time to disease recurrence for those patients, as well. So there are patients who are on the control cohort of surgery alone, and we'll be able to study that tissue in conjunction and compare those with patients who have received immunotherapy or nivolumab prior to their surgeries. So they have a number of biomarkers planned for the tissue that's being collected from the study.

Dr. Pal: Very interesting. Well, I can't wait to see the results, ultimately, of this trial. But in the meantime, Petros had outline some of the risks associated with immunotherapy in the context of the study he discussed. Anything to add to that, in terms of the risks that might be entailed in this trial?

Dr. Zhang: Right. So it is certainly a randomized trial, as Petros mentioned, so there are patients who are randomized to surgery alone versus patients who are randomized to the immunotherapy up front. So one dose of nivolumab followed by surgery and then maintenance treatment with nivolumab. And I fully agreed with the toxicity profile that Petros outlined very nicely. And when we get patients started on these immunotherapies treatments in clinic, I often talk about, we're activating your immune system, and therefore, toxicities can occur where the immune system is very active. So on the skin it can cause a rash, in the GI tract it can cause diarrhea or colitis, in a very small proportion of patients it can cause inflammation in the lungs or liver, and then, finally, it can affect their endocrine organs: the pituitary, thyroid, adrenal glands, and pancreas. And one more note about treatment with these immune checkpoint inhibitors of nivolumab, and other agents like nivolumab, is that these are really not for patients who have active autoimmune disease. We think that those patients who have active autoimmune disease requiring prednisone or other disease-modifying agents, those patients are probably going to have worsening of their baseline autoimmune disorder. So patients who do have that need to have a very close discussion with their providers before going on any of these trials.

Dr. Pal: Well, that's an excellent overview of toxicity, and again, just as I mentioned earlier, I certainly leave it in the hands of the patient and their respective clinicians to go through a very thorough discussion of toxicity, but I think that was a fantastic primer on it, Tian. Thank you for that. Before we close, I wanted to go to Petros for any additional comments on this concept of the PROSPER study. Petros, any additional thoughts?

Dr. Grivas: I think that Tian did a wonderful job summarizing all the key points. I think one of the key characteristics of this trial is, again, their rationale. The reasoning behind it, which as Tian mentioned, is we have the immunotherapy up front in the beginning of the treatment while the tumor is still present and the proteins, the antigens of the tumor, are still present, and that might be relevant in the recognition of those elements by the immune system when you give the immunotherapy. And then you have surgery, and then you have continuation of postoperative treatment, as Tian mentioned, and maybe that combination approach may be relevant. We have to see, of course, but I think it's a very, very compelling design that makes sense, at least scientifically speaking.

The other point, I think, is as [inaudible] already mentioned, this very [inaudible] teamwork, team effort from multiple investigators across the country. And that speaks volumes of the very nice design, as well as the collaborative in spirit, which I think is important for that patient to know, that people do work together to come up with these clinical trials. We all hope that this trial will keep accruing well and will end up with accrual target in order to answer this important question which is, as Tian mentioned, whether immunotherapy before and after surgery prolongs life and improves the times of cancer remission, which is important and clinically relevant question. And of course, it's a key point to have discussions about sometimes uncommon but significant immune-related reaction and go through the different nuances carefully with the providers when a patient's considering clinical trial. But clinical trials, as you mentioned Monty, is the way to develop new therapies and are very important part of a discussion in the routine patient care.

Dr. Pal: Excellent, Petros. Well, on behalf of Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang, I really want to thank you for joining our very first podcast from Cancer.Net. There's so many different clinical trials out there enrolling patients with genitourinary cancers, and we've only had time here to discuss 3 of them. If you have interest in participating in clinical trials, please do get in touch with your healthcare team. And of course, Cancer.Net serves as an excellent resource to communicate with experts in the field and learn more about respective genitourinary types of cancer. Thank you again for joining.

ASCO: Thank you, Drs. Pal, Agarwal, Grivas, and Zhang.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2019 American Society of Hematology Annual Meeting, held December seventh through tenth in Orlando, Florida. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams' disclosures at Cancer.Net.

ASCO would like to thank Dr. Williams for discussing this research.

Dr. Williams: Hello, and thanks for joining us for this podcast. My name is Michael Williams. I'm Professor and Chief of Hematology/Oncology at the University of Virginia in Charlottesville. And I'm pleased to discuss some exciting advances in lymphoma that were presented at the American Society of Hematology meeting held in Orlando in December 2019. My disclosures are that my research group here at the university, through the university, has received research support from pharmaceutical companies AbbVie, Pharmacyclics, and Janssen, and I have received honoraria for speaking at conferences from Xian-Janssen in China. So what I'm going to talk about today are 2 reports about the management of localized diffuse large B-cell lymphoma, an update on a novel therapeutic approach for relapsed mantle cell lymphoma. And then, I'll finish with a brief introduction of an agent that is showing promise for treating highly resistant relapsed lymphoma that was presented in the plenary session during the ASH meeting.

So let's start with localized diffuse large B-cell lymphoma. So DLBCL is the most common subtype among the many forms of non-Hodgkin lymphoma. Usually, people present with advanced stage disease. But as many as 25 to 30 percent may have a disease that's localized to just 1 site or a very localized area of lymph nodes, so these would be stage I or stage ll patients. And the first report that I'll comment upon was presented by Dr. Laurie Sehn at the BC Cancer Agency in Vancouver, British Columbia. So they did a retrospective review looking at 319 patients treated in British Columbia over the past 15 years. So these were patients who had a nonbulky mass, they were localized disease. And the treatment currently for this disease is that people get either 6 cycles of a regimen such as rituximab and CHOP chemotherapy or more limited chemotherapy. Typically, 3 cycles of R-CHOP followed by radiation therapy. The importance of this study is that it is exploring a mechanism to de-escalate therapy, if you will, by avoiding the use of the radiation therapy. So what they did, is patients with localized disease received 3 cycles of rituximab plus CHOP therapy and then underwent a PET scan.

So PET scans, unlike CT scans, are nuclear-medicine imaging that shows the functional uptake of radioactive glucose by the sites involved by lymphoma. So if you become PET negative after the three cycles of rituximab, CHOP therapy, then it seems likely that you've got a very highly responsive disease, and you may be able to avoid radiation therapy. So they did the PET scan after 3 cycles, and for those who were PET negative, then those patients received 1 additional cycle of rituximab CHOP, and that was the end of their therapy. If they were still PET positive, then they moved on to radiation therapy to the involved area.

So what they found was quite interesting that of the 319 patients, 254 were negative after their PET scan. And so went on, virtually all of them, to just getting 1 more cycle of rituximab CHOP as planned. The outcomes for those patients were that very few of them relapsed over the next several years. They followed patients now, for about four years or more, in most cases, and they found that the overall, 5-year progression-free survival was 88% for those who were PET negative. For the subset of patients who were still PET positive, and got the radiation therapy, their outcome was somewhat worse, in that there was only 74% who were still progression free. The overall survival for these patients was 90%, at 5 years, for those who were PET negative and 77% for PET positive.

So what this study shows us, is that a PET scan after 3 cycles, can inform us about patients who are 90% likely to have good control of their disease, with just 4 treatments, and you can avoid the exposure to radiation therapy. Those who were still PET positive still did well: 3 out of 4 were still in remission beyond 5 years but not quite as good an outcome. So these are patients who may be candidates for an alternative approach to try to do better with their long-term cure rates. So that leads us to the second presentation that I want to discuss.

This was presented by Dr. Daniel Persky on behalf of the Southwest Oncology Group, which is part of the National Clinical Trials Network, in the United States. So they had a very similar approach. They studied patients with localized Stage 1 or 11, nonbulky diffuse large B-cell lymphoma, and they got standard rituximab CHOP therapy, and then a PET scan after the third cycle. Just as in the paper I discussed from British Columbia. Those who had negative PET scans got one additional cycle of rituximab CHOP. Those who were still PET positive got involved-field radiation therapy and treatment with a radio-labeled monoclonal antibody. Essentially, a radioactive form of rituximab, which has given us a single dose about a month after they'd finished their involved-field radiation therapy and then they got a follow-up PET scan, thereafter.

So this study went on for several years, at multiple sites around the country. They enrolled 132 patients, and of those patients, 110 were PET negative after their third cycle. So only 18 needed to go on to this additional radiation therapy and the systemic treatment with the radio immuno therapeutic called Ibritumomab tiuxetan. They followed these patients now for 4 and a half years, and only 5 patients have progressed, and only 2 have died of their lymphoma. So of those who progressed, 3 of them had gotten just the R-CHOP alone. There was another patient who was PET positive but declined getting the radiation therapy who progressed. And then, another patient who had only 1 treatment was rituximab CHOP but then went off treatment due to toxicity. So similar, and in fact, almost identical to the British Columbia report. Five-year freedom from progression of their disease was 87%, and the overall survival was 90%. So these patients can do quite well, since many times, the location for localized DLBCL is in the head neck. There can be significant late effects of radiation therapy. So I think these studies reassure us that patients with localized disease can have very durable outcomes and cure rates. It's important to note that there's a higher rate of late relapse beyond three years in patients with localized DLBCL compared to more diffuse extensive disease suggesting that there may be some differences in the biology of a localized disease. So very important data, and data that gives us the opportunity to de-escalate treatment in localized large cell lymphoma.

So let's switch gears and talk about mantle cell lymphoma. There's been a lot of progress in this disease over the past decade. Much of it related to the use of nonchemotherapy targeted agents such as Bruton's tyrosine kinase inhibitors including ibrutinib and the Bcl-2 inhibitor, venetoclax. There was a study reported last year by an Australian group led by Dr. Constantine Tam. This study was updated at the ASH meeting with a longer follow up. So these were patients with Relapsed/Refractory disease, heavily pretreated. Many of them, previously, having had intensive chemotherapy and a stem cell transplant. And half of them had mutations in a gene called TP53, which is correlated with frequent chemotherapy resistance and high relapse rate. And what they found by combining the targeted agents ibrutinib and venetoclax, that they got very high response rates. The majority of patients responded although, there were a few who were primarily resistant, and about a third of patients, actually, got very deep remissions. PET negative and negative for minimal residual disease detection. If you look at the subset, of the highest risk patients, with the TP53 mutation, half of them achieved a complete response rate, and some of these patients have had durable responses. There have been a few patients who've had deep responses, who've been able to come off treatment. And overall, the duration of response at 2 and a half years is 74%.

But what this study shows us, is yet again, that these novel targeted drugs that are typically better tolerated than cytotoxic chemotherapy can have very good and indeed dramatic responses, and so is showing a lot of promise. It reminds us that in mantle cell, whether it's newly diagnosed or relapsed, that talking to your oncologist about clinical trial opportunities can often avail you of some of the most promising new approaches. And indeed, that's true for all forms of lymphoma, that clinical trial options should be part of the discussion with treatment planning.

I'm going to finish by just mentioning another novel agent that is being applied to patients with highly resistant relapsed disease. This is a molecule called mosunetuzumab, and this is a bispecific antibody. So there are a number of these now that are in clinical development, and some are FDA approved for treating leukemias and certain lymphomas. This one is designed to basically connect a body's immune system, the T cells, with the B-cell lymphomas by using an antibody that can recognize each of those and bring them physically together. So this was presented by Dr. Steven Schuster; it was a multinational study of this bispecific antibody in patients with very aggressive relapsed/refractory lymphomas including, diffuse large B-cell and transformed follicular lymphoma. And what they found in this study, is that response rates were 64%, with 42% of patients achieving a complete remission. So it's still early, but quite promising because these are patients who had failed CAR T-cell therapy. They may have failed transplant, or they were patients who needed a treatment to bridge them over to get to a CAR T or another treatment such as an allogeneic stem cell transplant.

The toxicities were generally manageable and similar to those seen with other bispecific antibodies. So it's early, but across subtypes of patients with aggressive and relapsed lymphoma, I think this is another promising molecule, that may well provide good therapeutic options via a clinical trial for patients who have very limited other options to manage their disease.

So thanks again for joining this podcast. There was a lot of other exciting data that we didn't have time to go through, so I encourage you to continue learning about what's new in the field, discussing with your oncologist, or with a consulting specialist in lymphoma, to make sure you can avail yourself of the best in current diagnostics and therapeutics. Thanks very much.

ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by the Conquer Cancer Foundation of ASCO, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses several studies presented at the 2019 San Antonio Breast Cancer Symposium, held December tenth through fourteenth in San Antonio, Texas. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. View Dr. Henry's disclosures at Cancer.Net.

ASCO would like to thank Dr. Henry for discussing this research.

Dr. Henry: Hello. I'm Dr. Lynn Henry from the Rogel Cancer Center at the University of Michigan. I would like to share with you a few of the research highlights related to breast cancer from the recent 2019 San Antonio Breast Cancer Symposium. I do not have any relationships to disclose related to these studies.

Many of the exciting trials that were presented at this conference were for treatment of HER2-positive breast cancer. This is a specific type of breast cancer that accounts for about 1 in 5 breast cancers. Both of the studies I'm going to discuss related to HER2 involve treatment of patients with metastatic HER2-positive breast cancer or cancer that has spread beyond the breast and surrounding lymph nodes.

The first trial is called HER2CLIMB. This is a phase III trial examining a new drug called tucatinib that is a pill that is designed to turn off HER2. Because of the type of drug that it is, it is thought to treat cancer both outside and inside of the brain which is important because many patients with this specific type of breast cancer can have the cancer spread to the brain. Patients who enrolled on this trial had previously been treated with multiple different treatments for HER2-positive metastatic breast cancer. In addition, almost half of the patients had metastases or cancer in their brain. In the HER2CLIMB trial, all enrolled patients were treated with the anti-HER2 antibody drug trastuzumab, also called Herceptin, as well as a chemotherapy drug called capecitebine or Xeloda. In addition, two-thirds received the new drug tucatinib and one-third received placebo. Overall, the drug combination was pretty well tolerated by patients with some diarrhea and fatigue. What is exciting about this trial is the patients who were treated with tucatinib had a longer time until their cancer progressed compared to those who took placebo. Those patients who had cancer in their brain got a similar benefit from the drug as those who didn't. In addition, on average, patients were also more likely to live longer if they took the tucatinib drug, an average of 4.5 months longer. This represents a potentially exciting new treatment option for patients with HER2-positive breast cancer. However, it has not yet been approved by the FDA.

The second trial called DESTINY-Breast01 tested another new drug also for HER2-positive breast cancer. This drug is called trastuzumab deruxtecan which is a standard HER2 treatment trastuzumab with a chemotherapy drug attached to it. This was actually a phase II trial in which all patients got the same dose of this new drug in the data that they showed at the meeting. Everyone had been previously treated with a number of different drugs for HER2-positive metastatic breast cancer. In general, patients tolerated the treatment relatively well although some experienced lowered blood counts, hair loss, and inflammation of their lung. In this trial, almost two-thirds of the patient had at least partial shrinkage of their tumor and the average length of time that patients were able to continue taking the medicine was more than a year. This drug also represents a potentially exciting new treatment option for patients with HER2-positive metastatic breast cancer although it also has not yet been approved by the FDA. We are hoping that both of these drugs will get approved in the near future.

Switching gears a bit, I will now mention a study that looked at a treatment for triple-negative breast cancer or cancer that is negative for estrogen receptor, progesterone receptor, and HER2 receptor. About 10% of all breast cancers are this type of cancer. A number of different trials have looked at using an oral chemotherapy drug called capecitabine beans or Xeloda for treatment of stage 1 to 3 triple-negative breast cancer. Studies have either looked at adding capecitabine to standard chemotherapy at the same time or using it as an additional treatment following completion of standard chemotherapy. However, to date, very few studies have shown that adding it is actually helpful. The investigators who presented their findings at the San Antonio meeting combined all the data from the trials that had been conducted so far, something called a meta-analysis. What they found was that specifically for the patients with triple-negative breast cancer, adding capecitabine to the treatment after the standard chemotherapy has been completed, decreased the likelihood of cancer returning and increase the overall survival of the patients. This was not the case for patients with other types of breast cancer including hormone receptor-positive and HER2-positive.

In order to maximize the benefit for patients and minimize the toxic effects of treatment, not all patients with triple-negative breast cancer should take capecitabine. Rather, those who have a higher chance of their cancer returning such as patients who get upfront chemotherapy and still have cancer left at the time of surgery should talk with their oncologists about whether capecitabine is a good choice for them.

One question that we cannot currently address is which patients are at higher risk for their cancer returning. In order to partially answer this question, a study was presented that examined compounds in the blood to see if they could be used to determine the likelihood of cancer returning in the future. Investigators looked at specific cancer compounds in the blood of patients who had been treated for stage 1 to 3 triple-negative breast cancer. Patients had blood samples drawn soon after surgery to look at both DNA from the cancer circulating in the blood, as well as cancer cells circulating in the blood. Those who had both DNA and cancer cells detectable in their blood were more likely to have their cancer return compared to those who didn't have either DNA or cancer cells in the blood. Those who had one but not the other were somewhere in between.

Although we currently don't know how best to use this information when caring for our patients, and therefore this is unlikely to be something that your oncologists will order for you at this time, tests like this are likely to become commonplace in the future once we have more data. One final study I would like to mention is related to estrogen receptor-positive breast cancer. The NSABP B-42 clinical trial is addressing the question of how long postmenopausal women with hormone receptor-positive breast cancer should be treated with aromatase inhibitor therapy. The investigators compared 5 years versus 10 years. The trial was completed a while ago. And now that they have followed patients on trial for a full 10 years, the investigators have shown that taking the aromatase inhibitor letrozole for 10 years instead of 5, reduced the chance of having breast cancer return in the future. However, the benefit was relatively small.

Therefore, since the benefit was relatively small and there is a risk of side effects from continuing to take the medicine, it is important for patients and oncologists to consider each patient's individual situation and risk of cancer returning when making the decision about how long she should take the medicine. In addition, there is more research going on that should provide additional information about how much benefit an individual patient is likely to get from this prolonged therapy. Overall, there is a lot of exciting research going on across all the different subsets of breast cancer.

As you can see, the results of many important clinical trials were reported at the recent San Antonio Breast Cancer meeting and there are many more clinical trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there is research going on that is examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Finally, there are even more trials going on trying to figure out how best to prevent breast cancer from occurring in the first place. Clinical trials are critical for the development of these new treatments.

Well, that's it for this quick summary of this important research from the 2019 San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you very much.

ASCO: Thank you, Dr. Henry. Learn more about breast cancer at www.cancer.net/breast. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Greg Guthrie: Hi, everyone. I'm Greg Guthrie, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Now as a reminder, Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. And today, we're going to be talking about coping with the fear of recurrence, and our guest is Hester Hill Schnipper. Hester is the emeritus manager of oncology social work at Beth Israel Deaconess Medical Center in Boston, and she now works in private practice. A two-time breast cancer survivor, she's a nationally known speaker, is active in numerous oncology organizations, and has written 2 books about breast cancer. Her daily clinical responsibilities include working with individuals, couples, and families living with cancer, and facilitating support groups. She's also a member of the Cancer.Net editorial board. Thanks for joining us today, Hester.

Hester Hill Schnipper: Thanks so much for asking me. It's a pleasure.

Greg Guthrie: It's a pleasure having you on with us here. So let's just start off with some basic questions so we're all on the right footing. What is cancer recurrence?

Hester Hill Schnipper: Cancer recurrence is a return of a cancer that was previously diagnosed. When all of us initially have a cancer diagnosis, part of the conversation includes what the general statistics, what the odds might be, how much we need to worry about a recurrence. But the truth is nobody ever knows with certainty what is or what is not going to happen, and all of us who have been through a cancer diagnosis and treatment live with some level of concern about the possibility of a recurrence. A recurrence, generally, not just for breast cancer, but generally for cancers is even scarier than the initial diagnosis because the initial diagnosis may well include the probability of treating for cure, whereas a recurrence generally means that the cancer is no longer curable, and the individual can anticipate just being on treatment for the duration of life.

Greg Guthrie: So this is a really common occurrence?

Hester Hill Schnipper: Well, it's more common than we would like it to be. Certainly, everyone wishes that you get through it the first time and you can truly be done with it. But none of us get a promise about that, and so all of us worry about the possibility of recurrence.

Greg Guthrie: And so most people are afraid of cancer recurrence, then this is kind of a frequent emotion?

Hester Hill Schnipper: I think so. And a very important thing for everyone to remember is this is a normal worry. I mean, cancer recurrences happen. It's not like being worried about, "Is there somebody hiding in my closet at 1 o'clock in the morning?" I mean, this is a genuine authentic thing to be concerned about. It's not a neurotic worry. It's real.

Greg Guthrie: Oh. And so what are some of the ways that this fear of recurrence can show itself?

Hester Hill Schnipper: I think people worry about it in a lot of different ways. And certainly, how intense the worry is is related to a number of factors. One has to do with the woman or the individual's actual medical situation. Again, how nobody gets a promise, but you know from the start that some people are more likely to have to face a recurrence than others just depending upon the specifics of the initial diagnosis and how well the first time treatment went.

People who deal with anxiety in their lives before they ever had cancer are of course going to be very anxious about this because it's the way they live and it's how they manage in the world. And now, they have 1 more very real and scary thing to be anxious about.

The way most of us experience it comes in thinking—hopefully not daily as some time passes—but thinking frequently about the what-ifs. So sitting around, say, a Thanksgiving table, and instead of just being glad to be there, also wondering, "Is this my last Thanksgiving?" Every ache and pain is experienced as a possible return of a cancer, the first thought being, "Oh, no. The cancer is in my back," as opposed to, "Oh, I should have gotten help moving all those heavy cartons yesterday."

It keeps some people awake at night certainly when we hear of a friend who has had a recurrence or even someone who has died of breast cancer or another cancer. That makes it scarier. People worry more before doctor's visits, appointments, before any scheduled scans, mammograms. Whatever their medical times and appointments are, those are certain to be moments to raise the fear.

Greg Guthrie: And how can people cope with or lessen these fears?

Hester Hill Schnipper: I think the first thing to say is that time helps. I think for most people, it doesn't go completely away but it absolutely gets better as some time passes, as you regain your physical health. When you look in the mirror and you look like yourself instead of a bald sick person, as life resumes its usual rhythms and busyness, cancer, most of the time, starts to recede into the background. Beyond that, the promise that it will get better. There are, of course, things to do that can help. And most people are helped by staying informed and staying connected. The reality is usually not as bad as what we might imagine. So really understanding what our situation is, complying with whatever the doctor's orders are. Some people continue on some kind of treatment past the usual chemotherapy, women with ER+ breast cancers. For example, staying on hormonal treatments for years or a decade or sometimes even longer. So complying with whatever the medical recommendations are.

The danger with thinking too much about the influence of lifestyle choices is believing that we are in control, that we can control it, because really we can't. I mean, by going through the prescribed medical treatment, we've done what we know we can do. And beyond that, there's some things that may tweak the odds a little around the edges, and those things include staying at a healthy weight, continuing a regular problem of mild to moderate exercise, eating a good diet, limiting your alcohol intake. Just living healthily in the ways we all know we should be living healthy anyway. They're not really special rules for cancer. They're the same rules that apply to good cardiac health or good any kind of health, but we just have different impetus to really pay attention to them.

Greg Guthrie: Right. And what are some of the ways that people can maybe build that acceptance of, "We can't control everything" in this situation?

Hester Hill Schnipper: Well, obviously, that's easier for some of us than others because some of us feel like we need to be in control of every single thing. And recognizing as life goes on, how little we really are in control in, I laugh off with my patients about how you get to choose what clothes you put on this morning and you probably get to choose what you have for lunch, but that's about it over the course of the day that you are really in control of.

So what can we do? Again, exercise helps not just in physical health but it helps most of us with mental health also. We continually hear about the fact that you know some kind of mindfulness or meditation practice is useful for some people. Other people enjoy adding Reiki or massage or Tai chi or some other sort of complementary alternative medical practice, but which makes them feel that they are doing something, and certainly is helping their general health, whether or not it turns out in the end to do anything that is cancer-specific.

I think it helps enormously to have cancer buddies. I always encourage people to consider a support group. If there are appropriate groups around, to consider talking to the woman you're sitting next to in the waiting room when you go in for your every 6-month, or however frequently it is, appointment, to perhaps continue participating in a cancer meeting, a conference of some kind, or a fundraiser. Some way to just to get to know other people who were living the same experience because we help each other more, I think, than anybody else can help us.

Greg Guthrie: Okay, great. So this kind of peer support is very important to helping cope with that?

Hester Hill Schnipper: Yes. I think it's very important. I mean, the downside, obviously, is the more people with cancer whom you know, the more likely it is that you're going to know some people who end up not doing well. So you have to get yourself to a place where the benefit of those friendships and the connections outweighs the possibilities that there may be scariness and loss in some of those relationships also.

Yeah, that's a really good point. So if we're coping with the fear of recurrence, sometimes is there something more needed than these coping methods? Is a treatment or intervention sometimes needed?

Hester Hill Schnipper: Right. Yes. And thank you for asking about that. My general simplistic rule about, "Should I be talking to somebody or would something else be helpful to me," is if you're wondering about it, it probably is a good idea to check it out. I think we all know ourselves better than anybody else knows us. And if we begin to be worried about ourselves or if we're not sleeping at night, if we can't concentrate on things, if we're not interested in the parts of life which usually please us, if we find that really our fear is paralyzing, even slightly paralyzing, we deserve to live better than that and it is important to get help. So how do you find help? There are clearly many wonderful therapists around who are great at what they do but really are not well informed about issues related to cancer. Places to start to look for somebody who is a competent therapist as well as somebody who is well-informed about cancer issues, certainly, talk to your doctor, talk to your treatment nurse, talk to your other cancer buddies. You can go on the website of AOSW, which is the Association of Oncology Social Work. And there is a public portion of that website where people can look up who might be nearby in their community who is sort of a psycho-oncology therapist. You can certainly call a nearby hospital or cancer center, ask to speak with an oncology social worker, and ask that person for referrals in the community.

Greg Guthrie: That's really great to give a sign for seeking help and then where to look for that. Are there other resources out there that can help people coping with their fear of recurrence?

Hester Hill Schnipper: I think, again, for most of us, information is helpful, and so you have to be careful about using the Internet and reading online. Certainly, ASCO's Cancer.Net is a wonderful website. I mean, Living Beyond Breast Cancer, NCI. I mean, there are many authentic and useful websites. I tell people, "Look for the .orgs or the .govs, and be a little less sure about the .coms, although some of them certainly are good too. Many of the cancer forums can be helpful in terms of sharing information, but they also can be terrifying and there's no way to be sure about the information that you're reading or hearing whether it's accurate or whether somebody is really crazy and just writing whatever he or she is writing. So I think going to the Internet in a prepared and thoughtful way, being careful about what you read, but being informed, staying current, understanding what's going on related to cancer world in general. And if there are specifics about your particular diagnosis, to be aware of what the possible survivorship issues may be, and are there new things coming around that you should know about?

Greg Guthrie: That's really great. I like this idea that a lot of the power comes from being informed and also from building some sort of support network that fits you. That seems like a good way to bolster yourself against this fear.

Hester Hill Schnipper: Absolutely, I think those 2 things with the addition of just the safe passage of time is what gets just about everybody safely to the other shore.

Greg Guthrie: Well, that's great, Hester. I think this information is going to be really helpful for our listeners, and I really appreciate you coming to share your insight and expertise here. Thanks very much.

Hester Hill Schnipper: Thanks very much for asking me [laughter]. Thank you.

Greg Guthrie: It's been great talking to you.

ASCO: Learn more about coping with the emotions that cancer can cause at www.cancer.net/coping. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In today's podcast, Dr. Ryan Nipp and Dr. Electra Paskett will discuss their article "Overcoming Barriers to Clinical Trial Enrollment," from the 2019 ASCO Educational Book. They discuss why it is important for people with cancer to participate in clinical trials and some of the reasons people may not be able to participate in clinical trials. They also discuss finding financial resources, the informed consent process, and the role of patient navigators.

Dr. Nipp is a gastrointestinal oncologist and health services researcher at Massachusetts General Hospital Cancer Center. Dr. Paskett is the Marion N. Rowley Professor of Cancer Research at The Ohio State University. She is the Director of the Division of Cancer Prevention and Control in the College of Medicine, a professor in the Division of Epidemiology in the College of Public Health, and the associate director for Population Sciences and Program Leader of the Cancer Control Program in the Comprehensive Cancer Center of OSU. She is also the director of the Center for Cancer Health Equity at the James Cancer Hospital.

Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology.

ASCO would like to thank Dr. Nipp and Dr. Paskett for discussing this topic.

Dr. Ryan Nipp: My name is Ryan Nipp. I work at Massachusetts General Hospital in Boston. I am a gastrointestinal oncologist. And I do research focused on palliative care, geriatrics, health services research. And I'm a part of the Cancer Outcomes Research team at Mass General.

Dr. Electra Paskett: I'm Electra Paskett. I'm at the Ohio State University. I am a Professor in the Department of Internal Medicine, College of Medicine. And I'm also the associate director for population sciences and a community engagement. And my research focuses on prevention, early detection, and working with survivors, mainly in terms of developing interventions to get people to do things to prevent cancer, detect it earlier, or live longer. And I have a specific focus in underserved and minority populations focusing on disparities.

Dr. Ryan Nipp: And we are talking about a podcast where we had done some discussion at this year's ASCO meeting about overcoming barriers to clinical trial enrollment. And we were just going to go through a few questions together and kind of give our thoughts on each of these. And the first question I wanted to ask you, Dr. Paskett, is why do you think it's important for patients to be involved in cancer clinical trials?

Dr. Electra Paskett: I would say for 2 reasons. First of all, we know that patients on clinical trials actually get very close monitoring, and so they would get the best of standard of care at their institutions. And secondly, the way that we progress in terms of knowing how to treat cancer, how to detect cancer early, and how to prevent cancer is through what we learn in clinical trials. Therefore, it's really important for all of us to participate in clinical trials so we can move the innovations and the new treatments and prevention strategies forward. And the only way to do that is through evidence from clinical trials.

Dr. Ryan Nipp: Absolutely. I agree. Just coming at this from a clinical standpoint as a gastrointestinal oncologist, we talk about this a lot in day-to-day practice where we have the standard of care option and then we have a clinical trial option. And as you brought out, that's exactly right. At the very least, everyone should be getting the absolute best standard of care and clinical trial. From our standpoint, the way we usually discuss it is it's what we're trying to do is advance knowledge, and this is, hopefully, going to benefit the patient currently, and then also, develop new knowledge for future patients. And ultimately, this is to advance the field forward. And that's one of the things I think is so exciting about oncology. The next question we were going to talk about was what are some of the barriers that might prevent a patient from participating in a clinical trial?

Dr. Electra Paskett: So I can start with a few from my perspective. We have studied this quite extensively, and we categorize the barriers into various levels. There are barriers at the patient level, barriers at the provider or the physician level, barriers at the health care system level, and then, we think, barriers even at the community or society level. And if we're talking about barriers at the patient level, a lot of times, patients don't know that there is a clinical trial available. And so that kind of affects their even ability to join a trial if they don't know that there is a trial open for them. Patients sometimes don't know a lot about clinical trials, and they're worried about clinical trials and don't quite understand what all that means. There are some myths about clinical trials using patients as guinea pigs. And that is not at all what clinical trial research is about. And so we do have to dispel some myths. And so those are some of the barriers.

There's also issues related to practical things like transportation and time. Sometimes, there are more visits that are entailed. And sometimes, people don't want to get an experimental drug. They just want to get the standard of care. However, the way clinical trials are designed, you always will get at least a standard of care. So you're not getting anything worse when you're on an oncology clinical trial. If we think of barriers at the provider level, sometimes the providers don't have enough time to talk about a clinical trial to patients because it does take some time to explain and to go through the consent process. But those are some of the reasons. And even if we move up to the system level, I like to call it, is that, sometimes, we don't have protocols available for every type of cancer that we see in every patient who has cancer. So I think that's a huge barrier. And then, a lot of times, the way the trials are written are that they exclude a lot of people, meaning a lot of people can't join because they're either too old or sometimes too sick or they already had 1 type of treatment started. So those exclude a lot of people and don't let them participate in clinical trials.

And then if we go up to the society or community level, there still are a lot of myths in our communities about participating in research, and we need to work hard to dispel those and make sure that all people are treated fairly in any type of research study. There's also, in some places, different policies about paying for the treatments that people receive on clinical trial. And we have to make sure that those barriers are also removed.

And the last thing I want to mention is that we know that children with cancer, almost 80% of those children with cancer go on clinical trials, whereas it's anywhere from 3 to 5 percent, sometimes 8% of adults with cancer that go on clinical trial. And the question is why is that? And there's a few reasons. The first is that there are very few types of childhood cancer versus the 200 plus types of cancers adults can get. So when you have few diseases, few cancers, you can develop protocols for the few. So there are many more protocols for the few cancers that children develop. Secondly, kids with cancer are usually treated at pediatric cancer facilities, of which there are few in the United States. So again, few diseases, few places that treat kids with cancer, and they treat them the same way. And all the people who treat kids with cancer have been trained the same way to know that putting a child on a clinical trial is the best treatment. So when you have similar standards, similar training modalities, similar protocols at these fewer institutions and fewer diseases, then you can have time and have the culture we talked about at the community level and at the provider level. You have the culture that we need to put these patients on clinical trials, and it facilitates accrual. So that's sort of a few of my thoughts about that question.

Dr. Ryan Nipp: Yeah. That's fantastic. I can't add a lot to that. I'll just kind of go into some of the specifics. You mentioned most of these already, like financial issues potentially representing a barrier from both the system level and from the patient perspective. When you choose to participate in a clinical trial, much like you were mentioning with the children, usually, it's a larger cancer center that offers the trial and requires travel and lodging for patients to get to the trial site. So that's also a time away from work and then just the burden of getting there and driving and paying out of pocket for those expenses. Not to mention, potentially with trials, there may be more frequent visits. So that could also add to the financial barriers.

And then just the only other point I would make is going into some more detail just from the clinician perspective, as you definitely mentioned, and it's very pertinent. The time it takes for discussing a clinical trial and going through the logistics, and in a time-limited visit, that's always a burden to try to get patients with enough information that you feel like you've given them what they need to know to make an informed decision about a trial, both the risks and the benefits, and then allowing you to also feel like you've understood the trial so that you can explain it to the patient. So there's a lot of work being done on how can we equip clinicians in the clinical setting so that we can make this less of a burden on that end so that you can identify patients a little easier, too, what trials might be available for them. And then, when they are identified as a trial candidate for certain trials, so that the clinician doesn't have to memorize 20 separate trials, you know what you can do. You can bring in potential trial navigators, something we'll talk about in a few other questions, where somebody who may know all the ins and outs of that specific trial so that you can at least introduce the idea of why scientifically this might make sense, but here's the very detailed logistics of what this trial is going to look like for that patient. So just wanted to go through a few of those higher level, more detailed issues, but it was incredibly thorough description of all the potential barriers.

The next question that we wanted to discuss was what are some of the resources that may be available for patients who are concerned about participating in a clinical trial for financial reasons? So we've done a lot of work on this at Mass General where, a few years back, we had looked at certain interventions where could we be identifying patients who are experiencing financial burden who may be at risk for not completing a clinical trial or not even being interested in the clinical trial just because of those financial issues that I mentioned about traveling to a trial site, having to take off from work, having to stay in a city or go to some farther place and then stay in a hotel just to be a part of the trial. We developed a program at Mass General, a financial assistance program, where people could enroll in their trial and then, once they got enrolled in the trial, if our social workers or nurses or the clinicians identified that the patient might benefit from financial assistance, they could be sent to this program, which we call the cancer care equity program. And at that time, patients would still pay for the travel and lodging, and then we had a system set up where we could reimburse them for travel and lodging. And we studied this, and we looked at our clinical trial accrual over the years before we had this program and then after the program. We have not currently done a randomized controlled trial with this program. That would be a future study that we would love to do. But when we just did this natural experiment seeing pre and post when we had this program, it did look like we saw an increasing clinical trial accrual at our institution during those years after the program was instituted. But obviously, without a randomized trial, there's many reasons that could contribute to that.

We also then, later on, gave patients surveys over time while they were participating in a clinical trial asking them about their financial burden over time just to see how are these patients' financial burden evolving over time on a trial, because you worry about when someone signs up for a trial, at that moment, they're willing to do anything just to get the appropriate best possible treatment. And then what happens with their finances from that point forward, you might not be thinking about from the beginning. So we surveyed a group of people who were enrolled in our program with financial assistance, and then we surveyed a group of control or usual care patients who were not getting the assistance but who were also on a clinical trial. Again, not a randomized trial for this, but we did see a trend where the group who was in the program had steady to improved levels of financial burden, whereas the group that was not getting the financial assistance, their financial burdens appeared to get worse over time. So that was some more evidence that having these financial assistance programs may help.

And this is a growing idea in the community, but there's a lot more research that needs to be done there. Some other evidence or some other things that we can be doing, at least at the clinical level or for patients when they come to a clinic right now, that where we don't have studies like that open, I would argue that, at the very least, it would be helpful for patients to know kind of what's required of the trial, how often are the trial visits going to take place, what's going to be entailed in those visits, how long are those daily visits when they do come to the clinic for their trial visit, how long are they going to be there, things like that just so you can plan ahead and kind of know how much of an effort is this going to take. And then there's also resources at many community or many cancer centers where you can have social workers or community resources available to talk with patients about what other resources might be available to help with either financial assistance or just knowing what the expenses may be related to the supportive care medications, related to the trial, related to the labs and things like that just so that taking a little bit of the uncertainty out of the picture so that people have an idea of what may be to come and being able to plan ahead.

Dr. Electra Paskett: Those are really great suggestions. And we have a very small grant from a foundation to provide up to $250 financial assistance for any cancer patient. And they have to qualify. There are income guidelines that qualify them. And we are just inundated with requests from our cancer patients. And this is irrespective of a clinical trial, but a lot of our patients are on clinical trials. And we can give them up to $250 each year. And the things that we might think are a little bit to help with gas or food or to get out of the parking lot are huge things to our patients. And I think that, sometimes, we don't fully appreciate the issues that our patients face when they come here to receive care. And I think being very astute and aware of that and trying proactively to, A, identify them. And we do that with our patient navigators. And it's actually a financial navigator that we have now that administers this money. And so being aware, asking about it, because it will make people, A, adherent, but B, just really one little thing from the stress that they're dealing with in being diagnosed and treated with cancer.

Dr. Ryan Nipp: Absolutely agree. The next question for us to discuss is what do we think is important for patients to know about the informed consent process?

Dr. Electra Paskett: Okay. So it is a process. That was your last word. Process. And a lot of times, we forget that it's a process. And we researchers sometimes just think about the informed consent document, but it's really a process. And the informed consent document or the consent form is a part of it. And it is a big part of it, but people need to be informed about the research. And I think it's very important when we, first of all, craft our consent forms, that they need to be in English, not in medical terms. They have to be in a good reading level, 5th to 8th grade if possible, and we should inform the patient by going through the subheadings on the consent form. And somebody needs to walk the patient through the subheadings on the consent form. A lot of consent forms, especially for treatment trials, have pictures to show the different treatments. And we definitely need to walk patients through the consent form, let them ask questions. If they want to take the consent form and talk to their family about it, we need to let them do that. But it really is an informed consent process, and we have to let that process occur.

Dr. Ryan Nipp: Agree, 100%. The other issue I think about in clinic when we're doing this is, often, we're doing informed consent, at least as oncologists, when we do routine chemotherapy. And when you're doing a routine chemotherapy consent, you're usually talking about the potential risks and benefits. And with most routine chemotherapy, they've been through trials already, so we have an idea of what those potential risks and benefits could be. Something I should have mentioned earlier, one of the things that I think is interesting related to the barriers, like Dr. Paskett was mentioning, where if the patients that we enroll on trials are younger and healthier than real life, then you do have a little bit of variation as far as when you see a patient in clinic, they may look a little different than what the clinical trial population looked like. So that gives a little bit of a gray zone of do we absolutely know what the risks and benefits are? But then, when it comes to a clinical trial informed consent process, that's where I think there's some interesting ethical dilemma that you're in some ways that we run into where you would love to give people the potential risks and know exactly what to expect, and you'd love to be able to give the potential benefits, but that's somewhat the essence of a clinical trial where we don't quite yet know what the benefits will be. We hope that there's going to be benefits. That's why we design the trial the way we do. And so you can kind of go through those potential benefits, but you also don't want to overplay it and give false hope. And then, on the other hand, when you're talking about the risks, you want to be realistic and say that this is a treatment, and based on the mechanism, it could cause these risks, but we're not 100% sure. That's partly what we're going to be studying with the studies. So I find that an interesting part of the informed consent process when you're talking about a clinical trial where you're gaining new knowledge, and that's part of what you will be gaining are the risks and the benefits that you can inform future patients when this is no longer on a study and is part of routine care.

Dr. Electra Paskett: Yep. Those are great points. And it's not meant to scare people, but it really does. People need to be informed.

Dr. Ryan Nipp: And then the last question for us was how can patient navigators help patients overcome some of the barriers to enrolling in cancer clinical trials?

Dr. Electra Paskett: So we've done a lot of work in patient navigation. And we use navigators now in many of our clinics. I talked about our financial navigators. But our navigators are people who are our laypeople, and they, a lot of times, come from the same background as the patients. And so they're able to gain trust of the patients and explain treatments in clinical trials and the things on the consent forms we've just been talking about to patients in a language that, sometimes, we as medical professionals don't use. And so navigators can help with that. And the job of navigator is to identify and then address the individual barriers that a patient has to completing their recommended treatment given them by their health care provider. And that's what navigators do. They can assess what the individual barriers are. And sometimes, they might be things like transportation. They might be childcare or eldercare or things like that. And the navigators have the resources and the connections in the institution and out in the community to address the individual barriers that a patient has. And every patient has different barriers. And so doing this intake assessment allows the navigators to identify and then tailor their strategies to each individual.

Dr. Ryan Nipp: Yeah. And then just to add on what I've kind of been learning from you, Dr. Paskett, is financial navigators are, essentially, there to make the entire process more streamlined and smooth for the patient as well as, potentially, the clinician as we're going through this process. It's always nice. One thing I find that's helpful about a lot of the clinical trials when we have patients on them is that what comes along with a lot of clinical trials is that you also have the resources that come along with the trial, which are the research assistants or the research nurses who are helping schedule things and keeping things organized. And that's one of the things that I could see as a clinical trial navigator to have just another set of resources, another set of eyes paying attention to the details, which can only help. It's one of these amazing potential interventions where it's almost all we're doing is trying to help. And so one of the points I wanted to make is I think we need a lot more research in this area. And I think it's ripe for research, but it's also one of those things where it's a little complicated, a lot like when we had done the financial assistance program where you think almost anyone could benefit, so then you have this difficulty with randomizing because everyone, you would hope, would have access to this, but that's currently not the standard, and that's why I think we need to prove it with more research.

Dr. Electra Paskett: Right. I agree. And one of the things when we first started offering navigation was our providers said, "Oh. I don't have to do that [laughter]." And so that they can spend more time working on the medical aspects versus these other aspects that the navigators are very competent to address.

Dr. Ryan Nipp: Absolutely. Well, I think that's all the questions that we were expected to address. Any final thoughts, Dr. Paskett?

Dr. Electra Paskett: No. Thank you. This has been fun. Been fun working with you and ASCO and the meeting and this. It's great.

Dr. Ryan Nipp: Agree. Again, it's always a joy working with ASCO [laughter]. Thank you. Thank you, everybody.

ASCO: Thank you Dr. Nipp and Dr. Paskett. Please visit ASCO.org/edbook to read the full article. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

The European Society for Medical Oncology 2019 Congress was held in Barcelona, Spain, from September 27 to October 1. In this podcast, Dr. Ricardo Cubedo shares highlights from the meeting, including treatment advances in ovarian and lung cancer. He also discusses a new type of clinical trial known as "basket trials" and the ways they are changing the shape of cancer research.

Dr. Cubedo is the Head of Sarcomas and Hereditary Cancer with the Medical Oncology Service at MD Anderson Cancer Center Madrid. He is also a member of the Cancer.Net Editorial Board.

ASCO would like to thank Dr. Cubedo for discussing this research.

Dr. Ricardo Cubedo: Good day, everybody. My name is Dr. Ricardo Cubedo. I am a medical oncologist from Madrid, Spain, from MD Anderson Cancer Center Madrid, and I was among the 25,000 attendees coming from all around the world, attending the last European Society for Medical Oncology Meeting, which took place between 27 September and 1st of October in Barcelona, which is a very beautiful Spanish city by the Mediterranean sea. We had a record-breaking 3,900 scientific communications, so you can bet that there is a lot to choose from, but I have chosen for you 3 topics. Two of them are relevant on their own, and very important results, and the last 1 I think it goes beyond the results themselves, changing the way we figure out things in order to fight cancer.

The first item is the results of the PAOLA-1 trial, focused on advanced ovarian cancer patients. You know that ovarian cancer is the most lethal gynecological cancers, because we cannot cure it when it is diagnosed too late to remove it, usually because it is too widespread within the belly. Nowadays, those patients rely on chemotherapy in order to stop the disease, control their symptoms, and live longer. We usually use chemotherapeutics based on platinum as front-line treatment, which are just too toxic to use all the time. So the way we do it, we give the chemotherapy for some months, then stop, then used again when the disease starts progressing and the patient becomes symptomatic. Those months between one chemo period and the next one, are precious for ovarian cancer patients, because they can enjoy them free from both the burden of progressing disease and the side effects of platinum chemotherapy.

The new drug that was the center of the PAOLA-1 trial is called olaparib. It is a new non-chemotherapy drug that targets directly the DNA of the tumor cells. And what it does is to prevent the DNA in the tumor cell from repairing itself when it is damaged, and that ultimately leads to the death of the tumor cell. What PAOLA-1 researchers really wanted to know is if olaparib, the new drug, was useful to delay progression once the disease was already stabilized by chemotherapy, giving patients a longer period free from chemo between 1 treatment and the next 1. That seemed a good idea, because olaparib is given as pills and has few side effects. 800, more or less, ovarian cancer patients were recruited into the trial from several countries all across Europe and were divided into 2 groups. Group number 1 were treated in the standard fashion: that is, chemotherapy until the tumor stopped, and then, maintenance with a drug called bevacizumab, which already been proven to delay the need for further chemotherapy. That is the standard. In the group B, the second group, that was the experimental group, olaparib, the new drug, was used on top of the standard treatment. Once the disease was [ceased?] with chemotherapy, patients were put on olaparib, and the results were impressive. In the control group, the median time that the cancer took to reactivate was 16 months, one-six, but the group of women treated with Olaparib didn't need further chemotherapy for a period just shy of 2 years. Researchers even spotted a group of patients with certain mutations in the tumor DNA that achieved an astounding 37-month progression-free survival. Being able to delay a new period of chemotherapy for over 3 years is a big, big improvement for women with advanced ovarian cancer, and a very welcome new tool in our weaponry against the disease.

That was the first item I wanted to discuss with you. The second one is also a clinical trial, a big clinical trial, called CheckMate 227. You know, we oncologists like to give trials those funny names. This is a trial for lung cancer patients. It is a very large study. It is still ongoing in over 300 hospitals all over the world, also in America. The non-small cell variety of lung cancer is the most common subtype of the disease and a really ruthless one. Lung cancer kills, every year, more Europeans or Americans than any other malignant tumor. So it's no wonder that huge resources are devoted to research against this beast. Being such an aggressive disease, equally aggressive chemotherapy has been the cornerstone of its treatment, when the tumor has grown or spread beyond the reach of surgery. Again, the problem is that such overaggressive treatments like combination chemotherapy with 2 or 3 drugs at the same time, might put a temporary break on the disease but unfortunately at the expense of quality of life.

What the CheckMate 227 trial explores is the role of immunotherapy. Immunotherapy, I am sure you have heard about it, is a new field of anticancer drugs, non-chemotherapy drugs, that do not attack cancer cell themselves but, instead, use some kind of molecular trickery to shake our own immune system against the tumor. The combination of 2 of such immunotherapeutic drugs, which are called nivolumab and ipilimumab, was compared in this trial to standard chemotherapy. So 1 group received the usual chemotherapy, and the other group received no chemotherapy at all, but those 2 immunotherapeutic agents combined.

The results were eagerly awaited, probably the most expected results in the whole meeting, and were disclosed in Barcelona amidst much expectation at a fully packed hangar-sized conference room. The full size of the trial is suspected to be north of 2,000 individuals, but we already know what happened to the first 800 group of patients during a 2-year period, and the results are quite encouraging. Unfortunately, non-small cell lung cancer is still a deadly disease, because no matter which treatment patients received within the trial, less than half of them were still alive at the 2-year mark. But while only one-third of the patients treated with current state-of-the-art chemotherapy were alive 2 years after treatment, 40% reached the 2-year bar among those treated with immunotherapy. Moreover, and more importantly, there were hints of a small group within that 40%, approximately 2 out of every 10 patients, that stabilized for long periods of time. Something very similar, stabilization, was observed some years ago, when we started to use immunotherapy in melanoma patients. And we now know that many of those patients, stabilizing for many years, are now in fact cured, even with extensive metastasis widespread into many organs. So at first glance, CheckMate 227 results might not seem much, but they mean that, for the first time, we have proved we can treat advanced lung cancer patients without a single drop of chemotherapy, which means much better quality of life. And we have, also for the first time, a realistic prospect for a cure, more beyond mere wishful thinking.

So we have seen the results of a couple of trials which are what we call "practice changing," which means that many ovarian or lung cancer patients worldwide, should be treated in a different way, with better results, as soon as their oncologists attending the meeting fly back to their working sites.

Lastly, the third piece of information I would like to share with you proves we are now right in the middle of a medical revolution. It's not surprising if I tell you that the first thing an oncologist like me will try to figure out when faced with a new advanced cancer case is where it comes from, because we do not equally treat a breast cancer case, a stomach cancer, or lung cancer. Well, it has been so until recently. During the last decade we have learnt quite a bit about the nuts and bolts of cancer. Specific gene mutations and wrecked proteins are both the hallmarks of cancer cells and targets for new drugs. I will give you an example: several years ago researchers found a protein called HER2 on the surface of cancer cells in 2 or 3 out of every 10 breast cancer patients. What this protein does is to rev up the cell's machinery keeping it in constant multiplication and leading to fast tumor growth, so those were patients with very bad prognosis, as the tumor that grows rapidly, also spreads rapidly. But a new drug called trastuzumab was tailored to disable HER2, the protein that was accelerating the tumor cell, and that made a huge leap in the treatment of HER2-positive breast cancer patients. But the white-coated guys at the research labs showed us that HER2 was not only present in breast cancer, but also in subsets of gastric, lung, ovary, womb, bladder, colon, and head and neck tumors, which was quite surprising, because those are completely unrelated malignancies. Nowadays, trastuzumab, the breast cancer drug, is also used to treat gastric tumors and is beginning to raise interest in the lung cancer arena too.

Well, inspired by those facts, some brave oncologists began to think out of the box and wondered if all we really need to know is the mutations and other molecular characteristics of the tumors in order to select treatments targeted against them, no matter where the cancer comes from. To treat in the same way, a colon cancer, a thyroid cancer, a breast cancer, or a brain cancer, provided they have the same molecular basis. Well such ideas were so revolutionary, they raised a few eyebrows and a lot of skepticism, but, well, this is science and we do not dismiss ideas without some previous research. Thus, the so-called "basket trials" were designed and carried out. Patients in such "basket trials" were hand-picked based on specific mutations and put to treatment, just like one chooses ripe berries and collects them into the basket.

The result of such ground-breaking trials proved that the concept was right. In this Barcelona meeting, Dr. Christian Dittrich from Vienna presented us with the combined results of 2 basket studies: the SCOUT and the NAVIGATE trials. Both explore the activity of a new drug called larotrectinib, in patients with any kind of cancer, provided their tumors had a mutant form of a protein called TRK. When healthy, TRK proteins are essential for a healthy brain and nervous system. But once mutated, TRK leads to cancer in several organs. And that was the basis of the trial. The new drug, larotrectinib, is carefully designed to disable the mutated TRK proteins while sparing the healthy ones you need. Both clinical trials combined included, more or less 160 patients, from children under 1 year to 84 year old adults. The results presented at the meeting in Barcelona were rewarded with the general applause from the audience, because they were astounding. 80% of the patients responded to the drug, more than thee-quarters of them still without signs of any health deterioration 1 year after they were given their first dose. Such results are really remarkable, as we are speaking of a group of patients diagnosed with no less than 18 different types of cancer, treated with a single drug, many of them having failed to several previous treatments or resistant to any known therapy.

Those results are not practice changing, because we have to resolve a lot of questions first, but are very exciting because they open a new drug for cancer treatment.

After a good medical meeting you go back home with some answers. But after a really good one you collect many more questions than answers. Are we going to treat patients based on their tumor genetics instead on classical tumor types? How are new treatments to be combined? Which ones should be given frontline, which ones after progression? What genes should be checked in tumor biopsies on a routine basis? Are there late side effects still to be seen from the new drugs? When to stop maintenance treatments? Are some long-lasting responders really cured of their cancer? How are we going to pay for the new ultra-expensive fancy drugs, some of which are to be maintained for years, even lifelong? Many, many questions to answer.

One thing I assure you: these are thrilling times to be an oncologist. I thank you all for your attention.

ASCO: Thank you, Dr. Cubedo.

Listen to more research highlights from scientific meetings: subscribe to Cancer.Net Podcasts on Apple Podcasts or Google Play, or visit www.cancer.net.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Greg Guthrie: Hi everyone, I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. And I'll be your host for today's Cancer.Net podcast. As a reminder, Cancer.Net is the patient information website of ASCO, The American Society of Clinical Oncology. Today, we're going to be talking about some research highlights from the upcoming Supportive Care in Oncology Symposium. And my guests are Dr. William Dale and Dr. Joe Rotella. Dr. Dale is the Arthur M. Coppola Family Chair in Supportive Medicine at the City of Hope National Medical Center in Duarte, California. He is also the Cancer.Net Associate Editor for Geriatric Oncology. Thanks for joining us, William.

Dr. William Dale: Thanks for having me. I'm happy to be here.

Greg Guthrie: And Dr. Rotella is the Chief Medical Officer of the American Academy of Hospice and Palliative Medicine. Thank you for joining us as well, Joe.

Dr. Joe Rotella: It's nice to be here with you today.

Greg Guthrie: All right. Now, I also want to comment that William and Joe both served on the news planning team for this symposium, which means they helped select the studies that we'll be discussing on this podcast. So let's start off by discussing what is meant when we say "supportive care." William, what do you think when I say supportive care?

Dr. William Dale: So supportive care medicine, and we have a Department of Supportive Care Medicine here at City of Hope, focuses on providing quality of life considerations for patients in a multidisciplinary way to emphasize functional status, to emphasize overall health for patients. Within supportive care, almost any part of the multidisciplinary team could be included outside of the cancer-directed therapy itself. As an example, palliative care exists as a division within our department of supportive care along with psychology, psychiatry, interventional pain, social work and some others. So when someone says supportive care, I think of everything outside of the cancer-directed therapy that we might do on a multidisciplinary team.

Greg Guthrie: That's a great foundation to have before we jump into these studies. And the first one I'd like us to talk about is called "A pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy, also called CIPN." So Joe, what is chemotherapy-induced peripheral neuropathy?

Dr. Joe Rotella: Well, peripheral neuropathy is a nerve damage which is often associated with neuropathic pain which can be of 2 sorts: sort of a constant burning or a deep kind of pain, or it can be more of a sharp and shooting type of pain. But it's associated with the toxicity of some common chemotherapy drugs, particularly those related to platinum and the Taxol family of drugs. And so it's a pretty common side effect of pretty common chemotherapy that's given to people with advanced cancers and not an easy symptom to treat. The typical pain medications that we would use for any sort of pain, for example opioids, don't always work that well for neuropathic pain. And, of course, there are safety issues and other concerns around using opioids. The other medicines that are often used might fall in the class of the medicines like Gabapentin, or anticonvulsants. And they also can have quite a few side effects and are just not terribly effective.

So this study looked at a nonpharmacological approach to managing the pain of chemotherapy-induced peripheral neuropathy. Very interesting, they looked at a standardized Swedish massage technique applied to the lower extremity, and then they had a number of other less intensive massage therapies that were used as a control. And they gave this 3 times a week over 6 weeks, and they were actually able to show a significant reduction in the symptoms related to the chemotherapy-induced peripheral neuropathy, and that it actually was sustained for up to 6 weeks after the massage treatment had been completed.

So this was fascinating that we could apply what appears to be a low-risk treatment that seems to be free of significant side effects that falls in that category of complementary alternative medicine that is so appealing to patients, and that this actually showed results that lasted beyond the duration of the intervention. And the less intensive control interventions did not result in as much symptom improvement. So very interesting study.

Greg Guthrie: Great. William, what do you think of this study?

Dr. William Dale: You know, peripheral neuropathy is extremely difficult for patients to deal with in our treatments as Joe just pointed out, are kind of notoriously ineffective. It works for a few patients, but often it doesn't that well and the side effects are quite high. So looking for alternatives to medications is something that's on all of our lists. Too often patients, in some ways, either get medicines or they're left on their own devices. We don't really have good evidence base to tell them what to do. Even though this study is not huge, it was very well constructed. So we know what kind of massage was used, what kind of evidence we had, and that it had a longer-term effect. And I agree with Joe that it's really nice to have an alternative that we can say has evidence that we might let patients consider and that's outlined in a way that lets us say this was a causal relationship or at least seems to be that patients were put into these two groups and it really was the group that got this very specific Swedish massage that had these enduring effects. So it'd be great to see this in a larger group of patients and to know for sure if this will work from a wider group of patients, but as a starting point, to have an alternative to medications for such difficult-to-treat side effect with such quality of life implications is really exciting.

The other thing I would mention and ask Joe about is they make the point that, these are licensed professionals. These were people who were expert at doing this kind of intervention. And patients sometimes ask, "Oh, can I get this?" And it would be nice to say just like any other intervention whether it was a medication intervention or a procedural intervention to say, "This is the way that this has to be done," and very specifically, what the outcome is expected. Too often we give vague information to people when it comes to so-called alternative therapies. But this was very specific to people trained to do this, presumably in patients who have cancer.

Dr. Joe Rotella: Yes, I agree. It's actually important to have a sense of what the intervention is that is actually performing better, let's say, than control or better than placebo or better than no intervention. The more we can pin down exactly what works and what frequency, what intensity is needed to get the optimal results, the more we can treat this like we would a pharmacological therapy where we can say, "Here's precisely what I recommend for you. Here's the dose. Here's the frequency. This is where the evidence says you're likely to get the most benefit." And I think there are certain interventions in complementary alternative medicine where we're starting to get there, where we can actually say, "This technique works better than that technique." And I think that's when we can begin to bring it into the same sort of rigor that we do our pharmacological treatments.

Greg Guthrie: Yeah, that's really great, just having an evidence-based approach to complementary therapies. So let's move on to our next study which is called "Anxiety, depression, pain, and social support in a large representative cancer population." So what questions did this study set out to investigate?

Dr. Joe Rotella: This study started with the recognition that pain is a very common symptom in patients with cancer and actually looked at what are some associations with pain? How does it relate to the presence of anxiety and depression? How does it relate to whether people have good social supports or not? Can we start to get a sense of how these things all interrelate to modulate the intensity and frequency of pain? And this study was interesting because it really looked at over 11,000 patients. And it was looking at patient-reported information. These were patients who were undergoing treatment for anywhere from stage I to IV cancer who were using a tablet to record their symptoms and information in a large academic center. And through this large database, a lot of analysis could be done to determine what were the key drivers of pain or modulators of pain. And what they found was a number of things were independently associated with the severity of pain in these cancer patients, included the site of the tumor. For example, head and neck cancer versus gastrointestinal cancer. The degree or severity of the disease, how advanced it was. Race and ethnicity was a predictor, lower income, all of these were independently associated with severe pain.

But this study went a little further and looked at the effect of anxiety or depression and the level of reported social supports. And in all cases, if the patient reports high anxiety or high depression, it is associated with higher pain scores. But those could be further modulated by the degree of social support. So if a patient had low social support level as self reported, then the effect of the depression on pain was more. If they had anxiety and high levels of pain and the ones who had transportation issues, for example, tended to have even more pain. So with this really large database, we begin to get a sense of how these various factors interface. And it's not just a tumor type, it's not just a stage of the tumor, it's not just things like race, ethnicity, socio-economic status, but it's also the degree to which anxiety and depression are present and the degree to which there are social supports that can actually play a role in the level of pain that patients report. All of this would support this multidisciplinary holistic approach that we take in supportive care programs or when we're providing palliative care through a team. This really supports that concept that pain is not an island unto itself. The whole rest of the patients' experience has a big impact on how they experience pain.

Greg Guthrie: William, what are some patient takeaways from this study?

Dr. William Dale: Yeah, to pick up on Joe's great summary of this, so overall, sometimes we have big studies but we don't have a reason for those studies to be big other than we happen to have a lot of data. What was nice in this study was they used the fact of a large dataset to show how the various variables interacted with each other. So in many cases, you can say well, if someone has a lower income or comes from a certain part of the world, whether a city or in an urban area versus a more rural area, they have worse outcomes. But, of course, those are very non-modifiable things. And it's perfectly fine to say it, but then what do we do about it? What made me feel good about this study was they said, "Well, if you have anxiety and depression, you can approach the problem this way. You can start to take care of those modifiable issues and that will help you with pain." Or if they live in a remote location, you could identify transportation. If you noted that they were living alone, for example, and they needed more help in the home, you could get that support. We all sort of feel that in our field, intuitively, that those things matter and are important. But this really started to connect the dots between pain and these other factors and how we might start to both take care of patients better, but to also start learning and putting the causal picture together about how this works.

And to your question about patient outcomes, so the idea of patient-reported outcomes has become more common and I think for good reason to actually ask the patient, "What's going on? What's their experience? How are they feeling?" And this was nice because it put an emphasis on that. And in many cases as they reported—this was on tablet computers—patients and respondents to surveys will be more honest when they're talking to a computer than they were to people, especially if it's their oncologist. We know that they will often become nervous, that if they could tell the oncologist, "Oh, I'm having these other problems," that someone might stop their therapy. And so they don't want that to happen when they really need those outcomes so they can identify what's needed. So screening people for these problems, which we advocate for, this just emphasizes how important they are even for something as basic as pain management.

And 1 other thing I wanted to mention, and Joe may want to weigh in on this as well, was this may help explain why we've had this so-called opioid crisis. And I don't want to overemphasize it, but if every time someone reports pain, our first instinct is to give them a medicine, especially an opioid medicine, and just increase the dose. Without identifying all these other factors, it's just an "If I have a hammer," kind of solution to a problem, when really the multidisciplinary approach that palliative care and supportive care have always emphasized would do better even for something like the overuse of opioid medications.

Dr. Joe Rotella: William, I really agree with you on that. Actually, the founder of the modern hospice movement who really started the whole palliative care movement as well, Cicely Saunders, had a concept she called "total pain." And what it meant was that you may experience pain physically, but it is an experience that involves your physical being, your mental being, your social relationships, your spiritual concerns, that the whole person plays a role in how you experience pain. And whether we're prescribing an opioid or massage or a ride to the chemotherapy center, whatever else we're doing, that multidisciplinary approach that looks at all the experience of the patient, not just their physical experience, but what's happening not just in their body, but in their mind, in their heart, in their spirit. That's really the key to giving people the very best quality of life. And those interventions that are less physically oriented tend to be lower risk, they're tolerated well. It's just a question of getting that team engaged and providing that more holistic approach.

Greg Guthrie: That's really great insight into this study. So let's switch to our third and last highlighted study for this symposium which is called "Racial/ethnic disparities in hospice utilization among Medicare beneficiaries dying from pancreatic cancer." Before we delve deeper into the study, I think it's important if we define what hospice care is and what we may mean when we say disparities. So Joe, how would you describe these terms?

Dr. Joe Rotella: Sure. Hospice care is a particular form of comprehensive palliative care that's provided to people near the end of life. Palliative care, supportive care is appropriate at any stage of illness when patients may experience stress or symptoms. But hospice care is designed for those patients that are near the end of life. And in our country, we have a Medicare hospice benefit which is in myriad insurance benefits, which means that it's generally a care that is accessible to almost everyone who is designated as most likely to be near the end of life. The Medicare benefit actually requires a physician to predict that it's probably the last 6 months or so. And it's a very comprehensive form of palliative care. It's really the gold standard of care for people who are nearing the end of life. And so what's interesting about hospice care though is even though it's comprehensive palliative and supportive care with a team right where you live in your home, wherever you call home, a lot of people don't access it at all or they don't access it until very late. Nationally, the trends are that about half the patients with Medicare who die actually get any hospice care before they die. And of those who do get hospice care, half of them get it for less than 3 weeks. And so it's really not fully utilized. And we could do a whole separate podcast on why people don't fully use it.

But it's interesting then if it's sort of an underutilized service to try to determine either what drives that. And among other things, one way to try to understand it is to look at whether there are disparities. And by disparities, we mean, does 1 population seem to be treated or seem to be having outcomes that are different from another population who only differ, let's say, in race or ethnicity or gender? And so this study is trying to look at is there a difference in hospice utilization among Medicare beneficiaries who have a very specific condition? They're dying from pancreatic cancer. And again, large database looked at thousands of patients, and really, they were trying to see if there was an association between race or ethnic minority and the utilization of hospice before dying.

Pancreatic cancer is a high mortality illness, and in fact, in this study, something like 64% of the patients did die during the course of the study. And there was a difference. Those from ethnic and racial minorities were less likely to initiate hospice care before they died. What's also interesting though is that disappeared if you looked at the very short hospice stay. If you looked at the patients who only got hospice for 1 or 2 or 3 days before they died. In that case, you don't see a racial disparity. But for that earlier hospice care, you do.

This study can't explain why, but it really raises questions around why. Is it about how we present the option? Is it because there are different preferences for treatment near the end of life? Is it socioeconomic factors? Don't know from this, but what we can show here is just like with so many other parts of healthcare, there are in fact important disparities here that we should try to understand.

Greg Guthrie: William, what are your thoughts on this study?

Dr. William Dale: It's such a complicated story of why there are differences between groups. And this study has a great job of showing that we see these differences. I will reflect on my own personal experience of being in 2 different places with 2 different populations. First in Chicago where we had a mix of largely African-American patients and white patients, and now in Southern California where we have a group that's roughly one-third white, one-third Hispanic and one-third Asian. And just to take a simple thing like that, we all noticed differences in the communities with acceptance of the terms of hospice and end of life care. And I think we've all wondered gosh, it does seem like certain groups get it more often than others for a variety of reasons. And to have some data and a large dataset to show, that's really a good thing for us, so that we can advance to the next step of what are the reasons for that or as Joe just said, why is that? I note in the general population, about two-thirds of people when you ask them at the end of your life, what is your preferred location for dying? And two-thirds will say at home. And then when you look at the actual likelihood of where people die, it's about one-third that dies at home and about two-thirds that are in the hospital.

Dr. Joe Rotella: Just to add a little bit more, there was something interesting kind of a side observation, and that is that in this particular study, although there was that disparity, overall, 74% of the patients actually did receive hospice care before dying. And so that's actually much better than that 50% or so that you see across the board for all people with all serious illnesses. And another set of disparities we might want to look at sometime besides race and ethnicity would be disease-specific disparities. Why do cancer patients have a higher rate of hospice utilization than patients with end-stage kidney disease, for example?

Dr. William Dale: Yeah, that's a great point, Joe. And it makes me think of our ultimate goal when we talk about people having certain goals for their care including their end of life goals. And we use the term "goal-concordant care" so that people pass away where they want to. But boy, that is a moving target sometimes. And so it's helpful to just see well, where do we usually end up in terms of goal-concordant care. And cancer patients, I don't know what you think Joe, do tend to end up in hospice more often, but I still think the length of stay are pretty short even in the cancer population.

Dr. Joe Rotella: I think that's true. And a lot of times, I think it may have to do with when the patient stops taking chemotherapy or some other direct cancer treatment. And in many cases, that's close to the end of life, and so then the stay is short.

Dr. William Dale: Yeah, I think that's right. I do point out I'm at a cancer center. Our name is City of Hope. And so patients come here with that sense of their coming with hope for something. Usually some form of a new treatment or almost a miracle treatment that will rescue them. And we in the field are often trying to make sure patients understand hope for, can be hope for lots of different things. My old mentor, Bob Arnold, used to say hope for higher quality of life. Hope for meaningfulness. Hope for comfort. All should be part of the conversation. So broadening, again, beyond just the hyper focus on what can we do about this disease to a broader set of questions is probably the next thing we need to understand.

Dr. Joe Rotella: Yeah, that'd be a great podcast [laughter].

Greg Guthrie: Well, I wanted to say I've heard the terms quality of life, multidisciplinary, and overall health a lot in our discussion today. And I think that that really just underwrites the role that supportive care plays in cancer treatments. And I think that that's just a great way to summarize the really interesting research that's coming out of this year's Supportive Care in Oncology symposium. So William, Joe, thank you for coming onto this podcast to talk about these studies and to show how they can help start to make improvements in patients' lives. I really appreciate you taking the time to join us.

Dr. William Dale: Well, thank you, Greg. We're looking forward to seeing these studies discussed at the conference.

Dr. Joe Rotella: It was a pleasure. Thanks so much.

Greg Guthrie: Thank you.

ASCO: Find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

The 2019 World Conference on Lung Cancer was held September 7 to 10 in Barcelona, Spain. In this podcast, Dr. Vamsidhar Velcheti will discuss a study presented at this meeting that looked at the effects of a new drug targeting a specific genetic change, or mutation, in some people with non-small cell lung cancer.

Dr. Velcheti is Associate Professor and Director of Thoracic Medical Oncology at NYU Langone's Perlmutter Cancer Center. He is a member of the Cancer.Net Editorial Board and is also the recipient of a 2012 Young Investigator Award and a 2015 Career Development Award from Conquer Cancer, the ASCO Foundation. Dr. Velcheti has no relationships to disclose related to this drug.

ASCO would like to thank Dr. Velcheti for discussing this topic.

Dr. Velcheti: Hi. This is Vamsi Velcheti. I'm the director for the Thoracic Medical Oncology Program at NYU Langone Hospital. And it's my pleasure to discuss an abstract presented at the World Lung Cancer Conference in 2019 in Barcelona. And the abstract I'd like to discuss is treatment with Amgen 510, Amgen five, one, zero, which is a highly selective potent KRAS G12C inhibitor. This was the data presented by Dr. Ramaswamy Govindan at the World Lung Cancer Conference in Barcelona in 2019.

So KRAS G12C appear as mutations in lung cancer are the most common driver oncogenic mutations. And, in fact, KRAS G12C was one of the first driver oncogenic mutations that was identified in non-small cell lung cancer. However, despite our several efforts to target KRAS G12C with multiple different drugs, we have failed to develop an effective targeted therapy option for patients with KRAS mutations. And this is very much unlike other mutations like EGFR, ELK, ROS, RET. So these mutations have a lot of treatment options for patients with targeted therapy. But unfortunately, that's not the case for KRAS mutation positive lung cancer patients. And KRAS G12C inhibitors like for Amgen 510 have showed us a way forward in terms of developing more effective targeted therapy treatments.

So this abstract presented by Dr. Ramaswamy Govindan at World Lung Cancer Conference is a fierce one, the trial of AMG 510. And in this study, they enrolled all types of solid tumors and predominantly colorectal cancer and lung cancer patients with a specific subtype of KRAS mutations called KRAS G12C. That is a KRAS mutation in the code on G12C. And in this study, they have seen very promising activity, anti-tumor activity in patients with non-small cell lung cancer, especially harboring KRAS G12C mutations. So out of the 76 patients that are enrolled in the study, 34 patients were patients with non-small cell lung cancer harboring KRAS G12C mutations. And out of these 34 patients, there were patients treated in the dose escalation part of the phase I study, meaning they were evaluating the safety of the drug at low doses, and they were escalating the dose in the patient. And there were 15 patients in the study that were treated at the maximum dose that was planned. For the study, which was the 960 milligram dose. So out of our 34 patients that were enrolled in the study, 34 patients with non-small cell lung cancer, most of the patients were heavily pretreated with at least 2 lines of prior treatments. And they were refractory to prior treatments.

So after 34 patients treated with AMG 510, nearly half of the patients had a partial response to treatment. And this is a significant advancement in terms of targeted therapy for KRAS mutant lung cancers. In previous studies with other agents, we have not seen such dramatic responses. And a majority of these responses have been confirmed responses. And the study is very early, and the data presented so far was only from the phase I trial. And there are more patients being enrolled in the ongoing phase II trial with the Amgen 510 in patients with KRAS G12C mutations. And most importantly, this drug seems to be fairly well tolerated and with relatively few treatment-related adverse events. And most of the adverse events were like a grade 1 and 1, with the most common adverse events being diarrhea, nausea, and 1 case of anemia, but has a substantially better safety profile than most other chemotherapy options for patients. So this is a very encouraging study. And we are all looking forward to more of these drugs targeting KRAS G12C and certainly excited to see these early results. And hopefully we'll see more further validation of these exciting early findings in subsequent phase II trials. Thank you very much.

ASCO: Thank you, Dr. Velcheti. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. We're interested in your opinions about your preferred podcast format and content offerings, so we hope you'll take a few minutes to take our listener survey. Visit podcast.asco.org to find a link to the survey and help shape the future of the ASCO Podcast Network.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.