Oncology On The Go

In the first edition of a special 3-part podcast series, CancerNetwork® spoke with Daniel Morgensztern, MD; Mary Ellen Flanagan, NP; and Janelle Mann, PharmD, BCOP, about best practices for implementing recently approved bispecific antibodies into cancer care. Their initial discussion focused on the clinical trial results, administration protocols, and toxicity management strategies related to the use of amivantamab-vmjw (Rybrevant) for patients with EGFR-mutated non–small cell lung cancer (NSCLC).

Morgensztern is a professor of Medicine and clinical director of Thoracic Oncology in the Division of Oncology at Washington University School of Medicine in St. Louis. Flanagan is a nurse practitioner in the Division of Thoracic Oncology at Washington University in St. Louis. Mann is a clinical oncology pharmacist at Siteman Cancer Center of Washington University School of Medicine in St. Louis and manager of Clinical Pharmacy Services at Barnes-Jewish Hospital.

Morgensztern began by giving an overview of amivantamab’s mechanism of action and highlighting supporting data for the agent when administered alone or in combination with other agents. 

The FDA initially approved amivantamab monotherapy for patients with EGFR exon 20 insertion–mutant NSCLC in May 2021 based on data from the phase 1 CHRYSALIS trial (NCT02609776). Furthermore, the agency approved amivantamab/chemotherapy as frontline treatment for patients with NSCLC harboring EGFR exon 20 insertion mutations in March 2024 based on data from the phase 3 PAPILLON trial (NCT04538664). Findings from the phase 3 MARIPOSA trial (NCT04487080) also supported the FDA approval of amivantamab plus lazertinib (Lazcluze) for those with EGFR-mutant NSCLC in August 2024.

Additionally, Mann reviewed key dosing considerations as patients receive amivantamab via intravenous infusion. She detailed the use of premedication such as diphenhydramine (Benadryl) to supplement amivantamab while monitoring for toxicities during the initial infusion period, which may necessitate additional dosing adjustments. Flanagan added to the conversation surrounding infusion-related reactions by describing strategies for mitigating the risk of venous thromboembolism, cutaneous toxicities, and other adverse effects.

References

1. RYBREVANTTM (amivantamab-vmjw) receives FDA approval as the first targeted treatment for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. May 21, 2021. Accessed January 29, 2025. https://tinyurl.com/3d8wtu4m

2. FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed January 29, 2025. https://tinyurl.com/msw4u5yk

3. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed January 29, 2025. https://tinyurl.com/yxc8u8t4

In collaboration with KidneyCAN, CancerNetwork® spoke with Eric Jonasch, MD, a professor in the Department of Genitourinary Medical Oncology of the Division of Cancer Medicine, and the director of the von Hippel Lindau Center at the University of Texas MD Anderson Cancer Center in Houston, Texas, about the missions and goals of the Kidney Cancer Research Consortium.


Jonasch is the principal investigator of an effort, supported by a Department of Defense (DoD)–funded grant, that aims to improve the treatment of patients with renal cell carcinoma (RCC) by developing a network of clinical trial centers that have expertise in both developing and executing new research efforts. 


“We want to do the clinical trials that the industry wouldn’t do otherwise and do the trials that are going to allow us to gain knowledge faster,” Jonasch said. “We do this by, number one, using novel agents; number 2, using more efficient and innovative clinical trial designs; and, number 3, incorporating correlative studies, including biopsies and various other circulating biomarkers analyses that allow us to get smarter faster.”


Many of the ongoing and recently completed trials in the kidney cancer space focused heavily on immune therapy, utilizing checkpoint-blocking antibodies like nivolumab (Opdivo) and pembrolizumab (Keytruda) or CTLA-4–blocking agents like ipilimumab (Yervoy). Of the studies moving the space forward, Jonasch highlighted an ongoing phase 1b/2 trial (NCT05501054) evaluating ipilimumab, nivolumab, and ciforadenant (CPI-444), an A2A inhibitor, in RCC along with other trials.


During the discussion, Jonasch mentioned the initiative to incorporate biopsies in treatment more frequently, particularly through giving a pre- and post-biopsy to see how the results change during therapy. This approach gives investigators an opportunity to see how cancer cells interact with immune cells.


 Additionally, Jonasch stated that they wish to expand their efforts to the broader kidney cancer community, as currently, work in the consortium only takes place in 7 “ivory tower” institutions that may be difficult to access for some patients. One of the ways they’re combatting this barrier is through working with the Veterans Affairs hospital system. Once that effort is complete, Jonasch hopes the consortium will be able to start helping more patient groups. 


KidneyCAN is a nonprofit organization with a mission to accelerate cures for kidney cancer through education, advocacy, and research funding. You can learn more about KidneyCAN’s work here: https://kidneycan.org/

Reference


Beckermann K, Rini B, Haas N, George D, Jonasch E. Phase 1b/2 trial of ipilimumab, nivolumab, and ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma. Oncologist. 2023;28(suppl 1):S13–4. doi:10.1093/oncolo/oyad216.022.

In a conversation with CancerNetwork®, Shewetal Mehta, PhD, spoke about her research team’s focuses in moving novel brain cancer therapies down the pipeline as part of an early phase clinical trials program at the Ivy Brain Tumor Center.

Mehta, the deputy director and pre-clinical core leader at the Ivy Brain Tumor Center of Barrow Neurological Institute in Phoenix, Arizona, underscored a scientifically rigorous, patient-driven philosophy that drives her team members to deliver timely answers to those with brain cancer via work in a clinical lab and a pre-clinical arm. This collaboration helps identify therapeutic agents that may demonstrate activity in the brain while determining patient populations who are suitable to enroll on clinical trials.

As part of her institution’s early phase trial program, Mehta specifically highlighted work associated with a phase 0/1 clinical trial (NCT06072586) evaluating BDTX-1535, a brain-penetrant fourth-generation EGFR inhibitor, for those with recurrent high-grade glioma harboring oncogenic EGFR alterations or fusions.1 Investigators are incorporating liquid biopsy, sampling cerebrospinal fluid from patients on treatment to monitor potential evolutions or changes in brain tumors.

Regarding biomarker testing, Mehta described the roles that gene sequencing and immunohistochemistry can play in identifying targetable alterations in patients with brain cancer. She mentioned vorasidenib (Voranigo), which received approval from the FDA in August 2024, as an example of a targeted therapy that may be suitable for use in patients who are found to have actionable IDH mutations.

“Over the last year, we’ve seen that we were capable of not just doing these early phase clinical trials [but of entering] this phase of moving drugs into phase 3 [studies]. That’s exciting,” Mehta stated regarding her outlook on the current state of brain cancer treatment. “Right now, we are excited about these new classes of agents that are within the space, like the proteolysis targeting chimeras, protein degraders, and antibody-drug conjugates, which have shown amazing promise in the rest of the oncology space.”

References

1.        Study of BDTX-1535 in recurrent high-grade glioma (HGG) participants with EGFR alterations or fusions. ClinicalTrials.gov. Updated January 15, 2025. Accessed January 15, 2025. https://tinyurl.com/m6kwr2b3

2.        FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed January 20, 2025. https://tinyurl.com/25r9fkvy

CancerNetwork® spoke with Michael P. Bogenschutz, MD, director of the NYU Langone Center for Psychedelic Medicine and professor of Psychiatry at NYU Grossman School of Medicine, about psilocybin-assisted psychotherapy (PAP) in managing psychological challenges associated with serious cancer diagnoses following the publication of a pooled analysis of 2 phase 2 trials assessing the regimen in this patient population.

In these trials, 87 patients were randomly assigned 1:1 to receive either psilocybin first (n = 45) or control therapy with niacin or low-dose psilocybin first (n = 42) followed by crossover. A total of 79 patients completed at least 1 assessment after the first dose.

He began by touching upon the significance of the results, highlighting an improvement in multiple psychiatric symptoms including anxiety (P = .0049), depression (P = .0007), interpersonal sensitivity (P = .0005), obsession-compulsion (P = .0002), hostility (P = .009), and somatization (P < .0001). Then, Bogenschutz discussed the potential for PAP to reduce an unmet need for patients seeking effective medication to mitigate cancer-related psychological challenges, highlighting limitations of both antidepressants and anxiety medication in this population. 

Next, Bogenschutz discussed implementing PAP into clinical practice for patients with cancer-related psychological challenges. In particular, he expressed that integration could occur through in-house operation, which may build the capacity to provide PAP within cancer centers, or through a referral system to a licensed practitioner trained to administer psilocybin. 

Additionally, he described potential adverse effects associated with psilocybin use, highlighting acute mind-altering and sympathomimetic effects. He then expressed the importance of psychotherapy as a means of supplementing the use of psilocybin, which may help patients better attain positive mental health outcomes than with psilocybin alone.  He concluded by highlighting the lasting effects of psilocybin dosing, which may persist for months after a single dose, as well as areas for future research in assessing PAP. Specifically, he emphasized exploring ideal treatment parameters and the full psychopathological scope of the agent.

Reference

Petridis PD, Grinband J, Agin-Liebes G, et al. Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nat Mental Health. 2024;2:1408-1414. doi:10.1038/s44220-024-00331-0

Following the 2024 San Antonio Breast Cancer Symposium (SABCS), Paolo Tarantino, MD, and Matteo Lambertini, MD, PhD, co-hosted a live X Space with CancerNetwork® and spoke about updated trial findings that may impact the breast cancer treatment paradigm.


Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School. Lambertini is an associate professor and consultant in medical oncology at the University of Genova – IRCCS Policlinico San Martino Hospital in Genova, Italy.


Tarantino and Lambertini highlighted data from various studies that investigators presented at the Symposium, which included results on the use of treatment modalities such as antibody drug conjugates and CDK4/6 inhibitors. Some presentations of interest included the following:


·      Phase 3 DESTINY-Breast06 Trial (NCT04494425)

o   Patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer were assigned to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or physician’s choice of therapy.

o   Treatment with T-DXd improved progression-free survival (PFS) among patients with a time to progression on frontline endocrine therapy of less than 6 months (HR, 0.38; 95% CI, 0.25-0.59), 6 to 12 months (HR, 0.69; 95% CI, 0.43-1.12), and more than 12 months (HR, 0.67; 95% CI, 0.51-0.88).

o   PFS improved with T-DXd regardless of disease burden.

·      Phase 3 EMBER-3 Trial (NCT04975308)

o   Investigators evaluated 3 treatment arms—imlunestrant (LY3484356) monotherapy, fulvestrant (Faslodex) or exemestane (Aromasin), and imlunestrant in combination with abemaciclib (Verzenio)—among patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.

o   Across the overall population, imlunestrant monotherapy improved PFS compared with standard endocrine therapy (HR, 0.87; 95% CI, 0.72-1.04; P = .12).

o   Imlunestrant plus abemaciclib also showed a PFS improvement vs endocrine therapy across the overall population (HR, 0.57; 95% CI, 0.44-0.73; P <.001). 

·      Phase 2 SOLTI-VALENTINE Trial (NCT05569811)

o   Patients with primary operable HR–positive/HER2-negative breast cancer were assigned to receive patritumab deruxtecan (HER3-DXd) alone, HER3-DXd plus letrozole (Femara), or standard multiagent chemotherapy.

o   HER3-DXd monotherapy yielded a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%); the respective rates in the chemotherapy arm were 4.2% (95% CI, 0.1%-21.1%) and 70.8% (95% CI, 48.9%-87.4%).

o   Combining HER3-DXd with letrozole produced a pCR rate and ORR of 2.1% (95% CI, 0.1%-11.1%) and 81.3% (95% CI, 67.4%-91.1%), respectively.

In a conversation with CancerNetwork®, Rachel A. Millstein, PhD, MHS; Loren Winters, NP; and Amy Comander, MD, discussed their article titled Implementing a Multidisciplinary Lifestyle Medicine Clinic for Cancer Survivorship, which was published in the November 2024 issue of ONCOLOGY®. The authors detailed the implementation of a novel oncology-based multidisciplinary lifestyle medicine clinic that may help enhance the quality of life (QOL) among survivors of cancer.

Millstein is a psychologist in the Behavioral Medicine Program and an assistant professor in the Department of Psychiatry at Massachusetts General Hospital. Winters is an oncology nurse practitioner and assistant director of the Lifestyle Medicine Program at Massachusetts General Hospital. Comander is the medical director of Mass General Cancer Center-Waltham, director of the Breast Oncology Program at Newton-Wellesley Hospital, and director of the Lifestyle Medicine Program at Massachusetts General Hospital.

Millstein outlined the rationale for this publication on the development of a multidisciplinary lifestyle medicine clinic, highlighting a need to boost general awareness and support for lifestyle medicine consultations and health behavior change in cancer survivor care. Winters then explained how the multidisciplinary clinic works in alignment with 6 key pillars of lifestyle medicine, as team members aim to promote physical activity, plant-predominant diets, restorative sleep, stress management, avoidance of risky substances, and social connections to enhance QOL among cancer survivors.

Additionally, Comander highlighted how the lifestyle medicine program optimizes health and well-being by matching patients to the specific services they require, which may include the help of team members such as board-certified physicians, nurse practitioners, registered dietitians, and clinical psychologists. Millstein and Winters then detailed the improvements in health behaviors associated with 2 patient cases at their program, demonstrating the potential benefits of implementing broad and diverse lifestyle medicine tools in oncology-supportive care.

Looking ahead, Comander described the importance of addressing gaps in education, a lack of programs focused on areas such as weight management, and other barriers to the implementation of lifestyle medicine in oncology care. Finally, each author expressed her hope to see more colleagues, clinics, and programs incorporate lifestyle medicine as part of elevating QOL among survivors of cancer. The authors invite listeners to contact them if they would like to find ways to implement lifestyle medicine in their respective centers.

CancerNetwork® spoke with Natasha Bahri, MD, MS, and Daneng Li, MD, about their Hot Topics article titled Casting a Wide NET: When Is the Optimal Time for 177Lu-Dotatate Treatment?, which was published in the November 2024 issue of ONCOLOGY®. Their article focused on findings related to the use of 177Lutetium-Dotatate (177Lu-dotatate; Lutathera) in patients with neuroendocrine tumors (NETs) and whether these data supported the use of the novel radioligand therapy for this population.


Bahri is a PGY-5 chief fellow in Medical Oncology and Hematology at City of Hope National Medical Center in Duarte, California. Li is an associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center in Duarte, California, and a gastrointestinal editorial board member of ONCOLOGY.


Bahri and Li discussed findings from the phase 3 NETTER-1 trial (NCT01578239) assessing 177Lu-dotatate for those with inoperable, locally advanced or metastatic, grade 1/2 midgut NETs following progression on long-acting repeatable octreotide therapy. Although these findings established a significant efficacy signal with the radioligand therapy, Li noted that questions remained regarding the sequencing of 177Lu-dotatate alongside other therapies in the treatment landscape.


The conversation also covered efficacy, safety, and quality-of-life (QOL) data from the phase 3 NETTER-2 trial (NCT03972488), in which investigators assessed high-dose octreotide with or without 177Lu-dotatate among patients with locally advanced or metastatic, well-differentiated, somatostatin receptor–positive gastroenteropancreatic NETs. Although data showed improvements in efficacy with the 177Lu-dotatate combination, there did not appear to be significant differences regarding QOL outcomes between arms.


“We’re waiting for further long-term follow-up information as there was no difference in the QOL metrics. It’s important to think about how these patients’ goals align with the therapy that we’re giving, and if we’re not seeing a difference in the quality of life quite yet, [we need to] look at individual patients, see what their goals are, and match them up to the therapy that we’re giving them,” Bahri stated.


Although the NETTER-1 and NETTER-2 trials demonstrate “great” results associated with efficacy end points such as progression-free survival, the authors noted that it is crucial to weigh these benefits with the potential toxicities when determining suitable candidates for treatment with 177Lu-dotatate.


“There’s a lot of nuances in terms of who is the ideal patient that’s going to maximally benefit [while] minimizing any risk of serious toxicity in those patients. As a result of that, we’re helping to improve their outcomes to the highest bars possible, whether it’s quality of life or survival,” Li concluded.


References

1.        Strosberg J, El-Haddad G, Wolin E, et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427

2.        Singh S, Halperin D, Myrehaug S, et al; NETTER-2 Trial Investigators. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403(10446):2807-2817. doi:10.1016/S0140-6736(24)00701-3

CancerNetwork® spoke with Rachel A. Greenup, MD, MPH, an associate professor of surgery (oncology), section chief of Breast Surgery, and co-director of the Center for Breast Cancer at the Yale School of Medicine, about the rationale behind conducting a study evaluating the lived experiences among women of color following breast cancer mastectomy, as well as data collection strategies employed during the study and key themes outlined in questionnaire responses.

First, Greenup, senior author of the study, emphasized that disparities persist for women of color following mastectomy for breast cancer, both in those seeking breast reconstructive surgery and those choosing to forego it, which is an act called “living flat.” She explained that many of the stories behind these disparities were left untold, and this study was seeking to unearth them.

She then explained that women of color who underwent a mastectomy for breast cancer were sampled for the study. The patient population included women from her institution and survivors willing to share their experiences.

Expressing that her team strove to let the stories of these women speak for themselves, she discovered 2 major findings during her research. The first theme that emerged was a cultural stigma surrounding cancer diagnoses among minority groups, which impact knowledge of family history as well as timely screening, care, and support for their disease. The second major theme that her study revealed was spirituality as a driver for many of the decisions following mastectomy.

Greenup further emphasized a need for cultural, racial, and ethnic inclusion during clinical trials, which extends to anticipating differences in cancer developments among diverse populations. She concluded by encouraging all patients to share their family history of cancer, regardless of background, as it can impact screening and prevention measures.

“I would encourage all families and all individuals from different cultural backgrounds to share their family history of cancer. It has a critical impact in terms of screening and cancer prevention for other family members,” Greenup said. “It can be difficult to have those conversations, but it is information that can be powerful for future prevention.”

Reference

Khubchandani JA, Suttiratana SC, Washington R, et al. Living flat: stories from women of color after mastectomy. Ann Surg Oncol. Published online October 15, 2024. doi:10.1245/s10434-024-16337-y

CancerNetwork, in a partnership with KidneyCAN, spoke with 2 genitourinary oncologists, Elizabeth P. Henske, MD, and Jason Muhitch, PhD, about how advocacy and funding through interdisciplinary collaboration between patient advocates, researchers, and physicians have resulted in numerous clinical breakthroughs in kidney cancer. 

Henske is a professor of medicine at the Harvard Medical School, an associate member of the Broad Institute of MIT and Harvard, director of the Center for LAM Research and Clinical Care, and a physician at Brigham and Women’s Hospital and Dana-Farber Cancer Institute. Muhitch is an associate professor of Oncology, co-chair of the Genitourinary Translational Research Group, deputy director of Graduate Studies, and a member of the Department of Immunology at Roswell Park Comprehensive Cancer Center at Roswell Park Comprehensive Cancer Center.

First, the state of kidney cancer advocacy was discussed, with Muhitch emphasizing multidisciplinary collaboration and the role of conferences, such as the Kidney Cancer Research Summit (KCRS) and the International Kidney Cancer Symposium, in bringing these groups together. Henske emphasized the strength of the advocacy network for kidney cancer, particularly as a mechanism for exchanging information, offering patient support and education, and facilitating research.

Next, funding was touched upon, with Henske expressing her interest in conveying the importance and urgency of kidney cancer research to Congress. Muhitch agreed, suggesting that the meetings with congressional offices offer opportunities to explain how funding can impact kidney cancer outcomes and scientist training, as well as the strength of patient advocacy in influencing Congress.

Muhitch and Henske then discussed the Kidney Cancer Research Program, which has enabled significant increases in funding for kidney cancer research, helped to facilitate clinical breakthroughs for common kidney cancer types, and set a foundation for exploring different kidney cancer variants. The discussion then turned to encouraging research for renal cell carcinoma , which Muhitch expressed can be attributed to partnership award recipients who went on to conduct research evaluating biomarkers predictive of patient responses to immunotherapies. 

Regarding additional funding mechanisms, Henske and Muhitch discussed numerous private foundations providing smaller research grants. Henske explained that these smaller grants are instrumental in taking the first steps to explore rarer kidney cancer subtypes, with Muhitch explaining that the earlier funding can formulate research that leads to greater funding from the Kidney Cancer Research Program.

KidneyCAN is a nonprofit organization with a mission to accelerate cures for kidney cancer through education, advocacy, and research funding. Learn more about KidneyCAN’s mission and work here.

In a conversation with CancerNetwork® at the 2024 Annual Oncology Clinical Practice and Research Summit, Andrew M. Evens, DO, MBA, MSc, spoke about a session he moderated at the meeting, in which he and other panelists highlighted ongoing efforts to improve the quality of care for cancer survivors at his institution. 

Evens is the deputy director for Clinical Services at Rutgers Cancer Institute and the system director of Medical Oncology and the oncology lead at RWJBarnabas Health Medical Group. He is also the associate vice chancellor for Clinical Innovation and Data Analytics at Rutgers Biomedical and Health Sciences.

Evens contextualized the presentation by describing various gaps in care for survivors of cancer, particularly among adolescent and young adult populations or those who become “lost in transition” as they switch from pediatric to adulthood survivorship. He emphasized a growing effort to mitigate the risks of post-acute or late effects following prior anti-cancer therapy, which can include cardiac disease, lung disease, or increased infections associated with chemotherapy or radiation. 

As part of elevating the level of care for cancer survivors, Evens described the collaborative efforts across different departments at his institution, including medical, surgical, and radiation oncologists; pharmacists; nurses; pathologists; and members of the clinical research team. Other international research projects, including those formed in association with the National Cancer Institute, aim to elucidate the granularity of treatment-related toxicity, which may help inform better survivorship care strategies. 

“Survivorship includes many factors,” Evens said. “There are physical and emotional factors, and we want to do everything we can as a comprehensive cancer program, and to do what’s best for the patient in a holistic manner. [Beyond the] cancer, it also means the emotional factors and health behavior modifications. For the rest of their life, [we want to] help the patient in every way possible so they can live the most fruitful life. A high quality of life is what we strive for.”

Reference

Evens A, Cole P, Ligresti L, Manne S. Cancer survivorship: scale, scope, and partnerships for patient-centered care. Presented at the 2024 Annual Oncology Clinical Practice and Research Summit; November 15-16, 2024; New Brunswick, NJ.