Dr Bupathi on Updates in the Second-Line Management of Advanced RCC

Manojkumar Bupathi, MD, MS, medical oncologist, Rocky Mountain Cancer Centers, discusses updates in the second-line management of metastatic renal cell carcinoma (RCC), and anticipated research in this space.

The second-line setting for patients with RCC is rapidly changing, and the majority of treatment decisions are determined by the agents utilized in the first-line, Bupathi begins.

 (Welireg) for the treatment of patients with advanced RCC who were previously exposed to a PD-1/PD-L1 inhibitor and VEGF TKI.

The regulatory decision was supported by findings from the phase 3 LITESPARK-005 trial (NCT04195750), which evaluated belzutifan in the second-line and beyond for patients with clear cell RCC, Bupathi states. Notably, belzutifan has a different therapeutic mechanism of action than standard VEGF inhibitors, he notes.

In LITESPARK-005, the median progression-free survival (PFS) for patients with previously treated advanced clear cell RCC treated with belzutifan was 5.6 months (95% CI, 3.8-6.5) vs 5.6 months (95% CI, 4.8-5.8) in those who received everolimus (Afinitor). This improvement was statistically significant, with a hazard ratio (HR) of 0.74 (95% CI, 0.63-0.88). Moreover, the median overall survival (OS) with belzutifan was 21.4 months (95% CI, 18.2-24.3) vs 18.1 months (95% CI, 15.8-21.8) with everolimus (HR, 0.88; 95% CI, 0.73-1.07; 

In contrast, the CONTACT-03 trial (NCT04338269), which assessed the benefit of continued immunotherapy following progression on a prior checkpoint inhibitor found that atezolizumab (Tecentriq) plus cabozantinib (Cabometyx), did not improve PFS, overall survival, or response rates vs cabozantinib alone in patients with metastatic RCC, Bupathi reports. Although the trial did not meet its primary end point, debate over the potential utility of re-challenging with immunotherapy combinations in advanced RCC continues.

Other anticipated research in the second-line includes upcoming data on tivozanib (Tivdak) plus nivolumab (Opdivo), Bupathi continues. This combination could further impact the evolving treatment landscape for patients progressing on first-line immunotherapy, he explains. Overall, these findings contribute valuable insights into optimizing therapeutic strategies for advanced RCC, highlighting the need for careful consideration of treatment sequencing and the exploration of novel combination approaches to enhance patient outcomes, Bupathi concludes.

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Manojkumar Bupathi, MD, MS, discusses updates in the second-line management of metastatic renal cell carcinoma and anticipated research in this space.

Treating Patients With RCC in Community vs Academic Settings

Dr Bupathi on Treating Patients With RCC in Community vs Academic Settings

Manojkumar Bupathi, MD, MS, oncologist, Rocky Mountain Cancer Centers, co-chair, genitourinary (GU) research, US Oncology, the US Oncology Network, associate director, GU Cancer Research, Sarah Cannon, discusses treating patients with renal cell carcinoma (RCC) in community vs academic settings.

Bupathi begins by stating that understanding the differences between treating patients with RCC in community vs academic settings is crucial. Traditionally, the perception has been that the most innovative work occurs in academic centers, and that the community is less engaged in these innovations. However, it's vital to emphasize that most patients with cancer are treated in the community, and it is thereby essential for community oncologists to grasp both the latest drugs available for patients and the adverse effects that are associated with these drugs to help advance cancer care for these patients, he emphasizes. The significance of community oncology treatment and research is just as profound as that of the treatment and research endeavors by academic counterparts, motivating Bupathi to address this topic.

However, numerous challenges remain within this line of thought, Bupathi says. Insurance services and collaboration with colleagues, specifically specialists in different institutions, present hurdles. Unlike oncologists at academic institutions, who are part of unified institutions, community oncologists must overcome various barriers to ensure optimal patient care, he expands. Despite these challenges, Bupathi explains that significant strides have been made to better treat patients in community settings, and there have been successes.

For example, Sarah Cannon and US Oncology Research have a robust committee ofinvestigators who acknowledge that they are actively transforming and improving patient care by offering innovative therapeutic approaches, he emphasizes. Bupathi says that once novel therapies are identified, oncologists will be able to streamline the available treatment processes, identifying treatment sites capable of catering to the specific patient population best suited for a given drug, he concludes.

Manojkumar Bupathi, MD, MS, discusses treating patients with renal cell carcinoma in community vs academic settings.


Manojkumar Bupathi, MD, MS, medical oncologist, Rocky Mountain Cancer Centers, discusses the evolving treatment landscape of bladder cancer.

Although unmet needs exist in bladder cancer, the integration of maintenance therapy has improved survival outcomes for patients, Bupathi says. However, it remains unknown why some patients do not derive sufficient responses to available therapy. As such, improved treatment options are needed for this patient subgroup.

Utilizing genomic analyses and targeted therapy is promising in this patient population, Bupathi explains. Recent data from ongoing clinical trials have also demonstrated promise. For example, during the 2021 ESMO Congress, findings from the phase 2 NORSE trial (NCT03473743) demonstrated clinically meaningful responses with erdafitinib (Balversa) plus cetrelimab in patients with 

-altered, metastatic or locally advanced urothelial carcinoma.

Findings from the ongoing phase 1/2 EV-103 trial (NCT03288545) demonstrated frontline activity with the antibody-drug conjugate enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) in patients with locally advanced or metastatic urothelial carcinoma. Moreover, the combination of sEphB4-HSA and pembrolizumab demonstrated synergistic activity and tolerability in patients with previously treated metastatic bladder cancer, according to findings from an ongoing phase 2 trial (NCT02717156).

Investigational targeted therapies have also demonstrated encouraging efficacy in patients with bladder cancer. Ultimately, understanding the tumor biology of bladder cancer and identifying more specific targets will further advance this paradigm, Bupathi concludes.

Manojkumar Bupathi, MD, MS, discusses the evolving treatment landscape of bladder cancer.  



Dr. Bupathi on the Evolving Treatment Landscape of Bladder Cancer 

Manojkumar Bupathi, MD, MS, medical oncologist, Rocky Mountain Cancer Centers, discusses considerations for second-line treatment sequencing in clear cell renal cell carcinoma (RCC).

A main consideration in sequencing therapy for patients with RCC is knowing what prior treatment the patient received in the first-line setting, as this informs how they should be treated in the second-line setting, Bupathi says. For example, if a patient received pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in the first-line setting, they should not receive lenvatinib in the second-line setting. Likewise, if a patient received cabozantinib (Cabometyx) plus nivolumab (Opdivo) in the first-line setting, they should not receive cabozantinib in the second-line setting and require an alternative regimen, Bupathi explains.

Sequencing is becoming more challenging because clinicians do not have all of the necessary data to make informed decisions and several second-line drugs have been moved into the frontline setting, Bupathi concludes.

Manojkumar Bupathi, MD, MS, discusses considerations for second-line treatment sequencing in clear cell renal cell carcinoma. 


Dr. Bupathi on Considerations for Second-Line Sequencing in RCC 

Manojkumar Bupathi, MD, MS, medical oncologist, Rocky Mountain Cancer Centers, discusses the improvement in first-line treatment options for patients with clear cell renal cell carcinoma (RCC). 

Three studies have demonstrated the efficacy of novel treatment options for patients with clear cell RCC in the first-line setting compared with traditional drugs like (Sutent) or pazopanib (Votrient), according to Bupathi. 

For example, the phase 3 CheckMate-9ER trial (NCT03141177) enrolled patients with previously untreated, advanced or metastatic RCC, and randomized them to receive either cabozantinib (Cabometyx) plus nivolumab (Opdivo) or sunitinib. Additionally, the phase 2 CABOSUN trial (NCT01835158) compared the use of cabozantinib vs sunitinib in patients with locally advanced or metastatic disease. Finally, the phase 3 CheckMate-214 trial (NCT02231749) enrolled patients with intermediate or poor-risk disease and compared the use of a doublet immunotherapy regimen comprised of nivolumab plus ipilimumab (Yervoy) vs sunitinib.

When navigating among these available options, it is important to consider risk stratification, possible associated toxicities, and whether a patient has symptomatic disease, Bupathi explains. Furthermore, comorbidities can help guide clinical decisions in this population, Bupathi concludes.

Manojkumar Bupathi, MD, MS, discusses the improvement in first-line treatment options for patients with clear cell renal cell carcinoma. 

Manojkumar Bupathi, MD, MS

Articles

Dr Bupathi on Updates in the Second-Line Management of Advanced RCC

Dr Bupathi on Treating Patients With RCC in Community vs Academic Settings

Dr. Bupathi on the Evolving Treatment Landscape of Bladder Cancer

Dr. Bupathi on Considerations for Second-Line Sequencing in RCC

Dr. Bupathi on First-Line Treatment Options for Clear Cell RCC