Oncology On The Go

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.”

References

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.”

In a conversation with CancerNetwork®, Jessica Cheng, MD, spoke about her work in the growing field of physical medicine and rehabilitation (PMR) and how it may improve quality of life outcomes among patients with cancer.

Above all else, Cheng, an assistant clinical professor in the Department of Supportive Care Medicine at City of Hope, emphasized how supportive care through PMR aims to ensure patient function. By developing a whole-person approach that focuses on the musculoskeletal and nervous systems, those involved in the field may minimize adverse effects and help patients participate in day-to-day activities more easily. Additionally, Cheng highlighted how this modality can involve the efforts of a comprehensive multidisciplinary team including physical therapists, occupational therapists, and speech therapists as well as those involved in disciplines such as integrative medicine, neurology, and orthopedics.

As part of ensuring function in patients who undergo therapy for cancer, Cheng discussed the importance of integrating exercise into their care routines. She highlighted how exercise in preparation for surgery, stem cell transplantation, or other treatment modalities may help patients recover from their treatment more quickly and yield improvements in the pathologic complete responses and other outcomes.

In terms of the next steps for aiding the growth of PMR across the country, Cheng detailed ongoing plans for a trial assessing the utility of cancer rehabilitation in patients with breast cancer and gynecologic cancer undergoing chemotherapy before surgery. Adopting a catchphrase of “prehab for all,” Cheng said that she wants all patients to be armed with the knowledge of PMR so that they can gain control over their lives and be able to pursue meaningful activities during their treatment courses.

“I hope that oncologists and rehabilitation physicians alike will see that there’s an opportunity with cancer prehabilitation to enable [patients] to get their cancer treatment, get through it better, and recover better,” Cheng said. “That’s my hope: that this [field] will spread even more like wildfire than it already is.”

In a special co-branded episode between Oncology On the Go and the American Society for Transplantation and Cellular Therapy (ASTCT)’s program ASTCT Talks, Rahul Banerjee, MD, FACP, and Noopur Raje, MD, discussed the risk of secondary malignancies in patients with multiple myeloma who receive CAR T-cell therapy.

Banerjee is an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Center and an assistant professor in the Division of Hematology and Oncology at the University of Washington. Raje is the director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center and a professor of medicine at Harvard Medical School.

Banerjee and Raje spoke in the context of prior advisories from the FDA on the potential development of secondary T-cell malignancies in patients who receive CAR T-cell therapy for hematologic cancers. Specifically, the agency required a boxed warning for secondary T-cell malignancy risks for BCMA- or CD19-targeting therapies in April 2024.1 The conversation also touched upon reports of secondary malignancies in cases and trials such as CARTITUDE-1 (NCT04181827), in which second primary cancers were highlighted in 9 patients who received treatment with ciltacabtagene autoleucel (Carvykti).2 

Considering these reports and warnings, Banerjee and Raje emphasized shared treatment decision-making with patients after assessing the risks and benefits of CAR T-cell therapy compared with other agents like bispecific antibodies. They also reviewed optimal strategies for monitoring and referring patients based on the incidence of certain toxicities.

“[Treatment with] CAR T cells requires planning, and we need to have good control of the disease. We need to have 4 to 6 weeks of a lead time to get these effective treatments to our patients, so early referral is a good idea,” Raje said. “[For example], if you see chronic diarrhea in someone that is way out of the window of what you would expect, referring back to the CAR T-cell center is important so that we don’t miss some of these toxicities.” 

References

1. FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. News release. FDA. April 18, 2024. Accessed August 22, 2024. https://tinyurl.com/5n8pm5ca 

2. San-Miguel J, Dhakal B, Yong K, et al. CIlta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379 

In a conversation with CancerNetwork®, Brian A. Van Tine, MD, PhD, spoke about the FDA accelerated approval of afamitresgene autoleucel (afami-cel; Tecelra) for patients with metastatic or unresectable synovial sarcoma expressing MAGE-A4. He discussed the data from the phase 2 SPEARHEAD-1 trial (NCT04044768) supporting the agent’s use in this patient population and highlighted how this approval might pave the way for other potential developments in the sarcoma landscape.

Van Tine, a professor of medicine and pediatrics and a medical oncologist at Siteman Cancer Center of Washington University in St. Louis, detailed results from SPEARHEAD-1 leading to the FDA’s approval of afami-cel. Based on these findings and the agent’s potential availability as a one-time intravenous fusion, afami-cel may offer improvements in quality of life to patients with synovial sarcoma compared with standard treatment options such as chemotherapy.

Topline data from cohort 1 of the SPEARHEAD-1 trial showed that treatment with afami-cel produced an objective response rate of 43% among 44 evaluable patients, which included a complete response rate of 4.5%. Additionally, the median duration of response was 6 months (95% CI, 4.6-not reached). Of patients with a response, durable responses lasting for 12 months or longer occurred in 39%. 

In terms of other potential benefits following the accelerated approval of afami-cel, Van Tine said that the T-cell therapy may increase treatment access to specific subsets of patients. For those who are unable to relocate and live near certain treatment centers during their therapy, afami-cel may offer a more readily accessible alternative that can allow patients to undergo treatment at home. Van Tine also described how this accelerated approval may “open the gateway” for other advancements related to the use of afami-cel and similar agents in solid tumors.

 “We’re all working hard to get these therapies open at our institutions,” Van Tine said regarding the next steps for increasing access to afami-cel following the accelerated approval. “Knowing who [has] HLA-A*02–positive [disease], knowing who has synovial sarcoma, and being ready to trigger the screening for MAGE-A4 is in every patient's best interest. If you’re one of the patients who have synovial sarcoma, you need to know your status [to determine] how we’re going to integrate this into your care plan.”

Reference

Adaptimmune receives U.S. FDA accelerated approval of TECELRA® (afamitresgene autoleucel), the first approved engineered cell therapy for a solid tumor. News release. Adaptimmune Therapeutics. August 2, 2024. Accessed August 14, 2024. https://tinyurl.com/mw6k4hjh

CancerNetwork® spoke with Ritu Salani, MD, about the expanded FDA approval of dostarlimab-gxly (Jemperli) in combination with carboplatin/paclitaxel for patients with primary advanced or recurrent endometrial cancer.1 

Salani, a board-certified gynecologic oncologist and director of Gynecologic Oncology at the University of California, Los Angeles Health, discussed the clinical benefit the dostarlimab combination showed for patients with endometrial cancer, particularly those with mismatch repair-deficient (dMMR) tumors, in the phase 3 RUBY trial (NCT03981796). Data leading to the approval showed a statically significant progression-free survival (PFS) and overall survival (OS) benefit in patients with dMMR or microsatellite-instability high (MSI-H) endometrial cancer, as well as for those across the overall population.

Noting the significant impact dostarlimab had on survival benefit without significant added toxicity, which investigators reported as early as March 2023, Salani said it was “wonderful” to have a relatively short turnaround time in making the combination therapy available for patients with primary advanced or recurrent endometrial cancer. Beyond the particular benefit among patients with dMMR tumors, she expressed the need to improve outcomes for patients with mismatch repair-proficient (pMMR) or microsatellite stable (MSS) tumors, who did not experience as much of a pronounced benefit from treatment with dostarlimab.

Salani also addressed the role of immunotherapy in subsequent lines of treatment following frontline therapy. Being thoughtful about sequencing agents in this setting may be an optimal strategy to give patients the greatest survivability and quality of life. She also considered alternative treatment strategies for certain patients, such as those with pMMR tumors. 

“The thing that is interesting is the study highlighted patients who had residual disease or measurable disease present when they were getting this therapy, and that seems to be where the most significant impact [is],” Salani said. “Seeing more data on the right selection of patients will be really important. There are other avenues of treatment for these patient populations, particularly the pMMR population, where you might see some other therapies that may have an equally profound impact as immunotherapy. Maybe that will lend itself to leading immunotherapy for second-line treatment, if needed.”

Reference

FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. News release. FDA. August 1, 2024. Accessed August 15, 2024. https://tinyurl.com/mtr6tpyp

In a conversation with CancerNetwork®, Catherine J. Wu, MD, spoke about the ongoing development of cancer vaccines as a potentially “cross-cutting” therapeutic strategy for treating patients with cancer.


Wu, chief of the Division of Stem Cell Transplantation and Cellular Therapies and a Lavine Family Chair for Preventative Cancer Therapies at Dana-Farber Cancer Institute, and also a professor of medicine at Harvard Medical School, discussed how neoantigens may show promise as possible targets for immunotherapy, which may make it feasible to treat broad swaths of patient populations through vaccination. Specifically, she highlighted the KRAS mutation as a potential area of focus based on its frequent expression in diseases such as gastrointestinal cancers, myeloma, and other solid tumors.


Findings from previous studies published in recent years also appear to support further research on the use of vaccines to manage cancer. For example, Wu brought up a study conducted by Memorial Sloan Kettering Cancer Center, in which investigators evaluated the potential utility of a personalized RNA neoantigen for those with pancreatic cancer. Data from this study indicated that the median recurrence-free survival was not reached in patients with vaccine-expanded T cells compared with 13.4 months in those without vaccine-expanded T cells (P = .003).


“There have been very promising studies,” Wu said. “There are many conceptual reasons for why cancer vaccines would partner well with other forms of immunotherapy such as immune checkpoint blockade. Increasingly, one can envision how it can be coupled together with cellular therapy.”


In terms of other research, Wu described how ongoing efforts aim to meet various time and cost considerations as vaccine-based therapy becomes more widely adopted in the cancer field. She underscored the necessity of developing a rapid manufacturing process and deploying vaccines to patients as quickly as possible. Additionally, she highlighted the progress in developing mRNA-based vaccines in light of the COVID-19 pandemic, suggesting that this modality may hold promise in the management of cancer.

Reference


Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;618(7963):144-150. doi:10.1038/s41586-023-06063-y

CancerNetwork® spoke with Kamran Idrees, MD, MSCI, MMHC, FACS; Natalie A. Lockney, MD; and Milad Baradaran, PhD, DABR, about the potential utility of intraoperative radiation therapy (IORT) among patients with pancreatic cancer. The group detailed the design and mechanism, gradual technical advancements, and trial data supporting the application of this radiotherapy modality for this patient population. 


Idrees is the chief in the Division of Surgical Oncology & Endocrine Surgery, an associate professor of surgery, an Ingram Associate Professor of Cancer Research, and director of Pancreatic and Gastro-Intestinal Surgical Oncology at Vanderbilt University Medical Center. Lockney is an assistant professor in radiation oncology and the program director for the radiation oncology medical residency at Vanderbilt University Medical Center. Baradaran is the head of quality assurance operations and assistant professor in the Department of Radiation Oncology at Vanderbilt University Medical Center.


As part of this discussion revolving around IORT, the group outlined the optimal conditions for using this technique depending on the extent of disease resectability in patients. Specifically, Idrees categorized patients as belonging to one of 3 major groups: those with metastatic disease, those with resectable disease, and those with borderline resectable or locally advanced disease. When considering these factors, patients with borderline resectable disease may be suitable to undergo IORT in combination with chemotherapy, radiotherapy, and surgery. 


The conversation also focused on a particular case involving a patient with pancreatic cancer who received IORT at their institution. Based on the outcome of this case, they highlighted how multidisciplinary collaboration in combination with careful patient selection may offer surgical resection through IORT.


“[There] has to be a multidisciplinary team approach to carefully select these patients and [determine] who can benefit from this procedure,” Idrees said. “For the families and the physicians who are taking care of [patients with] pancreatic cancer, it’s valuable to obtain a second opinion, even if [the tumor is] initially deemed unresectable. What’s unresectable in one surgeon’s hands may be resectable in a different team,” he added.

In a conversation with CancerNetwork®, Nausheen Ahmed, MD, spoke about optimizing monitoring strategies for patients with B-cell non-Hodgkin lymphoma who undergo treatment with CAR T-cell therapy.


Ahmed, an associate professor in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center, discussed the possibility of offering more flexible monitoring periods for patients in the context of findings from a real-world study published in Blood Advances.1 Data from her study showed that the occurrence of new onset cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) was rare at more than 2 weeks following CAR T-cell therapy infusion. Additionally, late non-relapse mortality generally resulted from infectious complications.


The FDA implemented a Risk Evaluation and Mitigation Strategy (REMS) to help manage the risk of severe CRS and ICANS by requiring patients to reside within 2 hours of an authorized treatment center for 4 weeks following CAR T-cell therapy infusion.2 According to the study authors, this mitigation strategy may create significant barriers to CAR T-cell therapy access among certain patients and caregivers who need to relocate as part of a treatment plan. 


Findings from Ahmed’s study supported the development of individualized monitoring strategies depending on the stability of the patient. She and her coauthors proposed a 2-week monitoring period for patients while allowing for an optional increase to 4 weeks based on factors such as physician comfort and availability of local community oncology support. As Ahmed emphasized during the discussion, having flexibility in these monitoring periods could help mitigate financial and geographic obstacles preventing adequate access to CAR T-cell therapy among patients.


“There has to be more of a hybrid model of care. There has to be more involvement of our referring doctors or community doctors in detecting and managing these infections or working with the specialized center in order to bypass the [emergency room] and other strategies to help these patients,” Ahmed said. “If there is enough data to say that the patients do not need extra restrictions beyond 2 weeks, which is what our studies show, then reconsidering the requirements will be one step towards decreasing disparities in access.”

References


1.        Ahmed N, Wesson W, Lutfi F, et al. Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Blood Advances. Published online July 24, 2024. doi:10.1182/bloodadvances.2023012549

2.        Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor (CAR) T cell immunotherapies modified to minimize burden on healthcare delivery system. FDA. June 26, 2024. Accessed July 23, 2024. https://tinyurl.com/2m284rjy

At the 2024 Kidney Cancer Research Summit (KCRS), CancerNetwork® spoke with various experts in the kidney cancer field about potential advancements in disease detection and updated efficacy data on immunotherapy and other treatment strategies in patients with renal cell carcinoma (RCC).

Karl Semaan, MD, MSc, a postdoctoral oncology research fellow at Dana-Farber Cancer Institute, discussed the implications of findings related to the use of an investigational tissue-informed liquid biopsy epigenomic profiling tool for detecting sarcomatoid differentiation in RCC.1 According to Semaan, this method may avoid the sampling errors and spatial heterogeneity challenges associated with traditional biopsy strategies.


Additionally, Neil J. Shah, MBBS, an assistant attending physician from Memorial Sloan Kettering Cancer Center, spoke about data from a real-world study evaluating treatment patterns and outcomes in those with metastatic RCC following prior receipt of immunotherapy and tyrosine kinase inhibitors (TKIs).2 Data showed no differences in overall survival (OS) outcomes across different immunotherapy- and TKI-containing regimens. Based on these findings, Shah emphasized a need for additional novel therapeutic approaches to help improve outcomes in later-line settings of treatment.

Bradley A. McGregor, MD, director of Clinical Research for the Lank Center of Genitourinary Oncology and medical oncologist specializing in genitourinary malignancies at Dana-Farber Cancer Institute, highlighted findings from his presentation on a phase 1b study (NCT04627064) evaluating treatment with abemaciclib (Verzenio) in a pretreated metastatic clear cell RCC population.3 Among 11 patients who received abemaciclib, 1 had stable disease, 8 had progressive disease, and 2 were not evaluable for response. Additionally, the median progression-free survival (PFS) and overall survival (OS), respectively, was 1.8 months (95% CI, 1.5-1.9) and 9.1 months (95% CI, 2.1-15.3).


Although abemaciclib monotherapy yielded no responses in the study, McGregor highlighted the potential clinical utility of administering the agent in combination with other therapies. Findings from his presentation suggested that CDK4/6 inhibitors may demonstrate a synergistic effect when combined with HIF-2α inhibitors, which is a potential strategy that investigators are evaluating with belzutifan (Welireg) and palbociclib (Ibrance) combination therapy as part of the phase 1/2 LITESPARK-024 trial (NCT05468697).

References


1.        Semaan K, Zarif TE, Eid M, et al. Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma. Presented at the 2024 Kidney Cancer Research Summit; July 11-12, 2023; Boston, MA. Abstract 44.

2.        Shah N, Sura S, Shinde R, et al. Real-world treatment patterns and clinical outcomes of metastatic renal cell carcinoma patients post immune-oncology (IO) and Vascular Endothelial Growth Factor (VEGF) receptor targeted therapies. Presented at the 2024 Kidney Cancer Research Summit; July 11-12, 2023; Boston, MA. Abstract 36.

3.        McGregor BA, Xie W, Xu W, et al. Phase IB trial of abemaciclib in advanced renal cell carcinoma. Presented at: 2024 Kidney Cancer Research Summit; July 11-12, 2024. Boston, MA.