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.

In December 2023, the FDA approved belzutifan (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; P = .099).

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.