Oncology On The Go

As part of Oncology On the Go, CancerNetwork® spoke with Andrew M. Evens, DO, MBA, MSc, about developments in the treatment landscape for adolescents and young adults (AYA) with lymphoma. He highlighted collaboration between adult and pediatric oncologists that may better standardize treatment for this population. 

Evens is the deputy director for clinical services at the Rutgers Cancer Institute and system director of medical oncology and oncology lead at RWJBarnabas Health Medical Group.

Of note, Evens discussed an effort to “harmonize” efforts between adult and pediatric oncologists in treating AYA patients who may receive different treatment regimens, despite being similar in age. Furthermore, he highlighted 2 prominent trials that illustrated collaborative efforts from both adult and pediatric oncologists: the phase 3 SWOG S1826 trial (NCT03907488) and the phase 3 AHOD2131 trial (NCT05675410).

Regarding the SWOG trial, Evens highlighted the greater efficacy and tolerability of nivolumab (Opdivo) with doxorubicin hydrochloride (Adriamycin), vinblastine sulfate, and dacarbazine (AVD) vs the standard of care brentuximab vedotin (Adcetris) plus AVD. 

“You could say it was, generally speaking, a double winner. [The nivolumab combination] was more effective at 2 years; the progression-free survival [PFS] was greater than 90%, [which was] a remarkable output. When I say a double winner, it was also largely better tolerated. There was less neuropathy, [fewer] infections, and less sepsis [vs brentuximab vedotin plus AVD]. Surprisingly, to a certain extent, [there were] not many immune-related adverse events outside of thyroid [events],” Evens said.

Furthermore, Evens discussed how collaboration between adult and pediatric oncology has impacted developments in the AYA lymphoma sphere. He placed a particular emphasis on the efforts of the Lymphoma Research Foundation, which convened multiple AYA lymphoma symposiums and established an AYA consortium. He then outlined unmet needs for this patient population, which included mitigating late toxicities following treatment and addressing inconsistencies in guidelines for lymphoma treatment in the AYA group.

Evens then discussed mitigating disparities and addressing barriers to care, underscoring a need to navigate the complexities of treatment for a patient population with a myriad of stressors. He concluded by highlighting resources available to AYA lymphoma groups, which include educational, medical, and psychosocial resources to best educate patients and express to them that they are not alone. 

“At the end of the day, be an advocate. Be an advocate for yourself. Be an advocate for others and know that there are [many] resources and people out there to help. We want to make sure nobody has to go through this alone, and that they have the medical and other psychosocial resources available to them,” Evens concluded.

CancerNetwork® sat down with Kelley A. Rone, DNP, RN, AGNP-c, to discuss the importance of speaking compassionately and ensuring patient awareness when leading end-of-life discussions among those with gastrointestinal (GI) cancers. The discussion also focused on combating burnout in the clinic, using opioids to help manage pain and other symptoms, and educating all members of a multidisciplinary team on initiating end-of-life conversations with their patients.

Rone is an advanced practice nurse (APN) in GI oncology at the Mayo Clinic in Phoenix, Arizona.

As part of leading these end-of-life conversations, Rone emphasized the necessity of addressing the discomfort patients tend to feel when talking about the fact that they may die from their cancer. Speaking with these patients may involve being open about the possibility of terminating therapy early if treatment-related toxicity such as fevers, diarrhea, and pain outweigh any potential efficacy or diminish quality of life. Additionally, Rone highlighted how APNs may be more comfortable with speaking about death than other team members.

Rone also discussed the importance of managing fatigue and pain as patients near the end of their lives. In her role, she initiates education on pain management early in end-of-life care discussions to make patients feel more comfortable about receiving opioids for symptoms.

When working with other members of a multidisciplinary care team, Rone illustrated the challenge of having physicians understand that their treatments may fail in younger patients and helping other oncologists become more experienced in speaking about death with patients. Regarding the idea of mitigating burnout and maintaining one’s mental well-being, Rone described how her role has given her perspective on what is truly important about life.

“This [role] helps you appreciate the finality of life. You don’t get upset about [minor] things after you see a 39-year-old with metastatic cancer,” Rone stated. “You learn to have an appreciation for the good things and not dwell so much on the bad things.”

CancerNetwork® spoke with John Paul Diaz, MD, about uterine transposition, a surgical technique aiming to preserve fertility in women undergoing radiotherapy for pelvic tumors. Diaz is the chief of gynecologic oncology, director of robotic surgery, director of the Center of Excellence in Minimally Invasive Gynecologic Surgery at Baptist Health, and lead physician for Clinical Trials in Gynecologic Oncology at Miami Cancer Institute. 

Of note, Diaz discussed the outcomes associated with 2 procedures conducted at his practice, as well as challenges associated with the development and implementation of the procedure. Additionally, he spoke about the next steps in developing and raising awareness of the procedure.

Diaz foregrounded the discussion by highlighting the simplicity of the procedure, which he stated was similar to a hysterectomy. Unlike a hysterectomy, uterine transposition entails a temporary relocation of the uterus to the anterior abdominal wall, which preserves it for fertility while removing it from the radiation field.

Furthermore, Diaz described the collaboration between Baptist Health and Memorial Sloan Kettering Cancer Center, including a partnership with Mario M. Leitao, Jr., MD, FACOG, FACS, who holds the largest series in the United States in performing uterine transpositions. He explained that the collaboration was conducive for expanding patient populations that may benefit from this surgery.

Diaz then underlined outcomes related to 2 uterine transposition procedures he conducted at Baptist Health. He described a favorable outcome with one patient who had completed the procedure 3 months prior who may be able to become pregnant in the future. The second patient was undergoing radiotherapy, with plans to undergo the second stage of the surgery in following months.

Diaz then highlighted a distinction between uterine transposition and other fertility preservation measures in that it preserves the entire uterus so patients can still carry a child, whereas other radiation therapy techniques do not. He then highlighted patients who are eligible for this procedure, particularly among women who want to preserve their fertility with pelvic tumors requiring radiation that might otherwise sterilize the uterus.

Challenges related to the development and implementation of the procedure were discussed, with particular emphasis placed upon quality of life following treatment. Additionally, he emphasized the idea of patient-driven improvements in treatment outcomes, which he hoped could be applied to help more women preserve their fertility.

Diaz continued by emphasizing the novelty of the procedure, explaining that experiences with it are growing while surgery success rates increase with global collaboration and technique sharing. He followed by underscoring the primary goal of cancer eradication, stressing that treatment for progressing disease takes precedence over fertility, and in those situations, fertility may be compromised.

He further outlined key short-term outcomes in patients undergoing uterine transposition, particularly as they related to maintaining uterine perfusion and mitigating post-operative complications. For long-term outcomes, he highlighted the goal for patients to be disease-free and capable of carrying a live birth.

Additionally, Diaz underscored a challenge related to raising awareness for this procedure, highlighting efforts he has undertaken to inform surgeons in the colorectal cancer field about the availability of this procedure as an option for this patient population. He suggested that colleague identification of eligible patients, effective referral, and increased proliferation of procedure knowledge may be effective in overcoming this challenge.

Diaz concluded by highlighting next steps for the procedure as they relate to expanding access for patients, increasing knowledge of the procedure among physicians, and developing novel techniques for uterine preservation during radiotherapy. He highlighted the “exciting” development of this procedure, which he suggested might have been inconceivable a few years ago, in achieving better outcomes for young women diagnosed with pelvic tumors.

In a conversation with CancerNetwork®, Ginger J. Gardner, MD, FACOG, spoke about current research and advocacy efforts to improve clinical outcomes among patients with gynecological cancers. With diagnoses of gynecologic malignancies on the rise around the world, Gardner also highlighted the next steps for raising awareness in the field and addressing gaps in care.

Gardner is a gynecologic surgeon at Memorial Sloan Kettering Cancer Center, as well as the chair of the board for the Foundation for Women's Cancer (FWC).

According to Gardner, approximately 115,000 of those in the United States and 1 million patients across the world are diagnosed with gynecologic cancer. Additionally, she highlighted a growing incidence of uterine cancers, which included a 2-fold increase in mortality among patients who are Black in the United States compared with other populations.

As part of raising awareness in this patient population and advancing potential therapeutic solutions, Gardner described ongoing initiatives at FWC to facilitate collaboration among scientists, researchers, and gynecologic oncology providers to help improve outcomes. Regarding potential treatment innovations, she also highlighted clinical trials designed to assess various disease prevention methods and other therapies like targeted agents, PARP inhibitors, and antiangiogenic treatments.

Looking ahead, Gardner detailed other potential developments in the gynecologic cancer space that she is excited about. For example, she spoke about future efforts to further uncover the tumor biology and molecular heterogeneity associated with these malignancies, which may help providers optimize treatment plans for patients.

“We are seeing some impact in improvement for gynecologic cancers with innovation in many of our disciplines; that includes disease prevention and innovative modalities related to treatment, inclusive of surgical innovation, new targeted therapies, refining radiation treatment, and ultimately patient-reported outcomes. We need to keep our eye on the ball for where we’re going next,” Gardner stated. “It is hard to dial it into just 1 or 2 snapshots, but I am so thankful that we have this time together to talk about the importance of gynecologic health awareness and research because it is important that we raise this conversation.”

In a special co-branded episode between Oncology On the Go hosted by CancerNetwork® and the American Society for Transplantation and Cellular Therapy (ASTCT)’s program ASTCT Talks, Alexis K. Kuhn, PharmD, BCOP, spoke with Katie Bruce, PharmD, BCPPS, and Susie Long, PharmD, about the use of approved cell-based gene therapies for patients with sickle cell disease, beta thalassemia, adrenoleukodystrophy (ALD), and metachromatic leukodystrophy (MLD). These panelists shared the pharmacist’s perspective on ensuring quality care with these ex vivo gene therapies across all treatment phases, including mobilization, conditioning, and infection prophylaxis.

Kuhn is an ambulatory Pediatric Hematology/Oncology/BMT Pharmacist at the Mayo Clinic in Rochester, Minnesota, and an assistant professor of Pharmacy at the Mayo Clinic College of Medicine. Bruce is a pediatric clinical pharmacy specialist at the Sarah Cannon Pediatric Hematology/Oncology & Cellular Therapy program of Tristar Centennial Medical Center in Nashville, Tennessee. Long is a pediatric clinical pharmacist in the Blood and Marrow Team at the University of Minnesota Masonic Children's Hospital.

Specifically, the panelists spoke about the use of agents like elivaldogene autotemcel (Skysona) and atidarsagene autotemcel (Lenmeldy), which are FDA-approved for ALD and MLD, respectively. They also discussed the use of exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia), which the FDA approved for treating patients 12 years and older with sickle cell disease in December 2023. The conversation broke down each stage of treatment, detailing optimal strategies for the cell manufacturing and storing processes as well as the management of toxicities like cytopenias. They also reviewed key considerations during the post-infusion period that may help maximize the quality of life for patients after they complete their therapy.

“It has been so amazing to be able to be a part of gene therapy and gene editing,” Bruce stated regarding the potential long-term impacts of these treatments. “We have patients who are able to hold full-time jobs they never were able to have before. We have patients who are climbing mountains and backpacking through Europe, which would have never been an option before because their sickle cell disease would have prevented them from [doing] that…. It’s not an easy process, and it has a lot of steps for the patient to go through, but the reward at the end of it all is worth it.”

CancerNetwork® collaborated with CURE® to speak with Samantha Shenoy, NP, MSN, a nurse practitioner at the Cancer Immunotherapy Clinic of University of California San Francisco (UCSF) Health, about the role she plays when treating patients with multiple myeloma who are receiving talquetamab-tgvs (Talvey). Of note, emphasis was placed on managing treatment-emergent adverse effects (TRAEs) and toxicities that may impact quality of life.

Shenoy foregrounded the discussion by outlining the role of nurses in facilitating the management of toxicities and providing education to patients in both an inpatient and outpatient capacity. She subsequently discussed common skin, oral, and dermatologic toxicities, as well as how they impact patient quality of life. 

Furthermore, she touched upon taking an aggressive approach to addressing early-grade cytokine release syndrome (CRS), placing an emphasis on close adherence to UCSF clinical guidelines for treating it. Additionally, Shenoy acknowledged the possibility of neurological effects occurring as a result of treatment with talquetamab, although she stated she has not observed any in her experiences with using the bispecific. 

Shenoy disclosed talquetamab-related monitoring parameters, indicating that taste changes and weight loss were notable risks. Particularly for weight loss, she mentioned that she regularly checks in with patients about their eating habits and weight. Furthermore, methods for living with taste changes were discussed, which included recommendations for prophylactics, dietary modifications, and dry mouth remedies.

Shenoy continued by suggesting that the efficacy seen with talquetamab, particularly as part of a combination therapy, makes it an impactful agent. Citing her experience as part of the phase 1 TRIMM-2 trial (NCT04108195), where talquetamab was assessed in combination with daratumumab (Darzalex) in relapsed or refractory multiple myeloma, she claimed that combination therapies for bispecifics would become the new standard in this patient population.

She concluded by expressing her passion for educating patients about management strategies for multiple myeloma. Additionally, she further illustrated the sentiment through her experience witnessing patients continue treatment for several years while overcoming toxicities associated with talquetamab.

“I feel passionately about the fact that we can educate patients who are struggling at the beginning [to] hang in there. It is not going to last forever,” Shenoy stated. “I can imagine how frustrating it is [when you are not] able to taste, your mouth is dry, and your hands are peeling. Just know that it is not forever.”

Dholaria, BR, Weisel K, Mateos MV, et al. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated TRIMM-2 results. J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.8003

In a conversation with CancerNetwork®, Yoshie Umemura, MD, offered various perspectives on progressing in the brain cancer treatment field. In addition to detailing institution-level advances in delivering multidisciplinary care, she highlighted her personal growth as she advanced in the neuro-oncology field while giving key advice to aspiring researchers who are in the early stages of their careers.

Umemura, the chief medical officer of the Ivy Brain Tumor Center, division chief of Neuro-Oncology, and the William and Joan Shapiro chair of Neuro-Oncology at Barrow Neurological Institute, first described what drew her to studying neurology and eventually specializing in neuro-oncology, emphasizing the potential to form close connections with patients during treatment. Additionally, her collaborative approach to care and her institution’s emphasis on multidisciplinary practice have helped in yielding various accomplishments, which included expediting the development of an investigator-initiated trial during the COVID-19 pandemic.

The conversation also focused on the personal aspects of Umemura’s neuro-oncology career. Delving into her experiences with immigrating to the United States when she was a high school student, she recalled feeling like an outsider as she learned to speak English and began to study neurology. However, she noted how several role models and mentors in the field have offered her guidance, which helped her grow and take on more leadership positions over time.

Continuing to build upon the theme of collaboration in brain cancer research, Umemura emphasized the necessity of finding mentors even outside of one’s institution to advance in the field. Additionally, as part of paying it forward to a new generation of neuro-oncologists, researchers should also become open to guiding others once they have gained enough experience. 

“When you are at a conference and you meet someone you think you might click with, you’re intrigued about, or you’re impressed with, you can shoot an email and ask them if they would be open to chatting with you about a question or mentoring you,” Umemura said. “[You should also] pay it forward. Always be open to mentoring others; I think that’s the only way to move forward….It [speaks] to the collaborative aspect and how to operate as an outsider. You’re not an outsider as long as you make the connection; you can just wedge yourself in.”

CancerNetwork® spoke with James R. Berenson, MD, about the potential role that JAK inhibitors may play in the treatment of patients with multiple myeloma. The conversation focused on the rationale for researching this drug class as well as ongoing initiatives to assess the utility of agents like ruxolitinib (Jakafi) for this patient population.

Berenson, founder, medical and scientific director, and president and chief executive officer of the Institute for Myeloma and Bone Cancer Research and private practitioner in West Hollywood, California, described the factors associated with the overexpression of JAK in the bone marrow, which may constitute a prime survival factor for multiple myeloma. This overexpression may affect the checkpoint inhibitor proteins in the body, resulting in resistance to standard anti-myeloma therapies such as immunomodulatory drugs. 

Additionally, he mentioned a patient case that had involved a scenario in which JAK-mutated multiple myeloma progressed following prior treatment with lenalidomide (Revlimid). According to Berenson, the disease’s resistance to lenalidomide was primarily associated with proteins driven by JAK; subsequent treatment involving JAK inhibition proved successful in restoring the efficacy of lenalidomide. 

Based on a rationale to target JAK overactivity in the bone marrow and results from this patient case, Berenson and colleagues have focused on researching ruxolitinib as a therapeutic candidate for potentially improving outcomes in multiple myeloma via JAK inhibition. Findings from a phase 1 trial (NCT03110822), for example, have demonstrated that the efficacy and tolerability of ruxolitinib plus methylprednisolone can be extended with lenalidomide in those with multiple myeloma. Additionally, other ongoing trials aim to combine ruxolitinib with agents such as selinexor (Xpovio).

“The question is, where will ruxolitinib sit in the sequencing of treatment of [patients with] multiple myeloma? Where will selinexor be?” Berenson stated. “At this point, there's certainly been low use of these drugs, especially ruxolitinib in multiple myeloma. We hope, with a more positive signal, these drugs will move further up in the algorithm of how you treat multiple myeloma.”

Berenson JR, Limon A, Rice S, et al. A phase I trial evaluating the addition of lenalidomide to patients with relapsed/refractory multiple myeloma progressing on ruxolitinib and methylprednisolone. Target Oncol. 2024;19(3):343-357. doi:10.1007/s11523-024-01049-w

In a conversation with CancerNetwork®, Nader Sanai, MD discussed the current state of the glioblastoma field, highlighting ongoing research efforts to help improve outcomes among patients with this disease. 

Sanai is the director of the Ivy Brain Tumor Center and J.N Harber Professor of Neurological Surgery, Francis and Dionne Najafi chair for Neurosurgical Oncology, and chief of neurological oncology at Barrow Neurological Institute.

Specifically, Sanai described plans to assess treatment with niraparib (Zejula) compared with temozolomide (Temodar) in a population of patients with newly diagnosed MGMT unmethylated glioblastoma as part of the phase 3 Gliofocus study (NCT06388733).1 He contextualized the rationale for conducting this study by focusing on findings from a proof-of-concept hybrid study (NCT05076513) and detailing how they supported additional investigation into the utility of niraparib. 

According to findings from this proof-of-concept study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the median overall survival (OS) was 20.3 months among patients who received niraparib in combination with radiotherapy.2 Additionally, data showed that niraparib reached drug concentrations in Gadolinium-nonenhancing newly diagnosed glioblastoma tissue exceeding those of any other evaluated PARP inhibitors; investigators identified no new safety signals after combining niraparib with radiotherapy in this population.

With the Gliofocus trial, Sanai and co-investigators aim to provide a clinically meaningful quality of life benefit with niraparib-based therapy beyond a marginally valuable statistical advantage. By evaluating treatment with niraparib, investigators look to improve historical survival rates reported with standard-of-care options among patients with unmethylated disease.

“What we’re looking to do with this trial is set a benchmark that’s clinically relevant for patients and providers. The [OS] target for the study is 18 months, which is to effectively convert [a] 12-month natural history to a natural history closer to the methylated glioblastoma population,” Sanai said. “We think that is a meaningful transformation of a difficult patient population, a significant chunk of survival time that would be beneficial to patients, providers, and caregivers. Importantly, [it may also mean] an advantage for quality of life, which is of paramount importance for this patient population.”

1.        A study comparing niraparib with temozolomide in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma. ClinicalTrials.gov. Updated June 24, 2024. Accessed September 16, 2024. https://tinyurl.com/y25er8p9

2.        Sanai N, Umemura Y, Margaryan T, et al. Niraparib efficacy in patients with newly-diagnosed glioblastoma: Clinical readout of a phase 0/2 "trigger" trial. J Clin Oncol. 2024;42(suppl 16):2002. doi:10.1200/JCO.2024.42.16_suppl.2002

In a conversation with CancerNetwork®, Georgios Evangelou, MD, MSc spoke about his manuscript titled Neoadjuvant Capecitabine Plus Temozolomide in Atypical Lung NETs, which he and his coauthors published in the July issue of ONCOLOGY®.

Evangelou, a medical oncologist and consultant in the 3rd Department of Medicine at Sotiria General Hospital in Athens, Greece, reviewed the results of a case study involving the use of neoadjuvant capecitabine (Xeloda) plus temozolomide (Temodar; CAPTEM) for a 62-year-old woman with well-differentiated atypical carcinoid. The patient was asymptomatic at diagnosis, with imaging revealing an atypical bronchial neuroendocrine tumor (NET) as well as a pancreatic mass indicating another NET. 

This patient subsequently underwent treatment with CAPTEM, which resulted in minor volume reductions of masses in the left lower lobe and subcarinal lymph node after 6 months of therapy. Although the pancreatic mass increased in size, Evangelou and colleagues excised it via central pancreatectomy, allowing the patient to resume treatment with CAPTEM for 6 additional months and undergo lobectomy with lymph node dissection. Further use of CAPTEM produced a partial response in the mediastinal lymph nodes and a 21% reduction in the size of the primary tumor.

Following treatment, the patient was able to recover without any significant complications. Additionally, follow-up scans revealed no avid lesions, and there were no signs of disease recurrence at 24 months after the lobectomy. Based on the results of this case study, the authors noted how neoadjuvant therapy may significantly impact the management of patients with atypical carcinoids, although larger clinical trials may be necessary to affirm the potential survival benefit of CAPTEM.

“I hope that others will recognize the potential value of CAPTEM as a neoadjuvant treatment in similar cases. Sometimes, these cases are very difficult to manage; you need the neoadjuvant treatment because it can offer tumor shrinkage. Eventually, it can lead to radical excision of the disease,” Evangelou said. “We need larger studies to better understand the effectiveness of the regimen as a neoadjuvant treatment.”