Dr Choueiri on the Utility of Belzutifan/Cabozantinib in Advanced ccRCC

Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, discusses findings from the phase 2 LITESPARK-003 study (NCT03634540) of belzutifan (Welireg) in combination with cabozantinib (Cabometyx) for patients with advanced clear cell renal cell carcinoma (ccRCC).

At the 2023 ESMO Congress, investigators shared updated data from cohorts 1 and 2 of the phase 2 trial. Cohort 1 consisted of treatment-naïve patients with ccRCC who were treated with 120 mg of belzutifan plus 60 mg of cabozantinib daily. Cohort 2 consisted of patients with ccRCC who had received prior immunotherapy or a prior targeted therapy and were given 120 mg of belzutifan plus 60 mg of cabozantinib daily.

Choueiri reported that the overall response rate (ORR) in the overall patient group from Cohort 1 was 70%, and the ORR in the overall patient group from Cohort 2 was 31%. Furthermore, the median progression-free survival (PFS) in cohort 2 was 30.3 months (95% CI, 16.6-not reached), and the median PFS in Cohort 2 was 13.8 months (95% CI, 9.2%-19.4%).

HIF2 alpha inhibitors, including belzutifan, are a novel class of agents, Choueiri says. Previously, investigators observed favorable outcomes with HIF2 alpha inhibitors alone, however, LITESPARK-003 combined belzutifan with cabozantinib, a potent VEGF TKI, he emphasizes. In cohort 1, patients had manageable toxicity, which was addressed through dose interruptionsand dose reductions, particularly with cabozantinib, Choueiri notes. All 50 patients in this cohort experienced tumor shrinkage, and 70% of them exhibited responses, Choueiri says.

Cohort 2 encompassed patients who had received prior treatment with up to 2 lines of therapy, including those who had received a PD(L)-1 inhibitor. Investigators observed responses in this cohort regardless of whether the patients had received 1 or 2 lines of therapy, or if they had undergone immunotherapy alone or in combination with VEGF treatment, Choueiri emphasizes. The toxicity profiles in cohort 2 were similar to those in cohort 1, and 31% of these patients experienced responses, he concludes.