Dr Rini on the Background of the FDA Approval of Belzutifan in RCC

Brian I. Rini, MD, FASCO, Ingram Professor of Medicine, Division of Hematology Oncology, chief, Clinical Trials, Vanderbilt-Ingram University Cancer Center, discusses the background that led to the FDA approval of belzutifan (Welireg) for the treatment of patients with advanced renal cell carcinoma (RCC).

On December 14, 2023, the FDA granted approval to belzutifan for the treatment of patients with advanced RCC who have undergone treatment with a PD-1 or PD-L1 inhibitor and a VEGF TKI. The efficacy of belzutifan was assessed in the randomized phase 3 LITESPARK-005 trial (NCT04195750), which demonstrated a statistically significant enhancement in progression-free survival (PFS) with belzutifan compared with everolimus (Afinitor; HR, 0.75; 95% CI, 0.63-0.90; 1-sided P = .0008). The median PFS was 5.6 months (95% CI, 3.9-7.0) with belzutifan as opposed to 5.6 months (95% CI, 4.8-5.8) with everolimus.

Although overall survival (OS) data are still incomplete in the present analysis, with 59% of deaths reported, there is no observed trend indicating an OS disadvantage with belzutifan. Additionally, a descriptive evaluation of patient-reported symptom and functional outcomes favored belzutifan over everolimus.

The LITESPARK-005 trial predominantly enrolled patients in the third and fourth-line settings, representing a refractory population of patients with kidney cancer who had experienced disease progression on previous immune and VEGF TKI therapies, Rini begins. This patient population aligns with the typical profile of patients in such settings, he adds. Notably, although the PFS curves of each arm initially overlapped with each other, indicating no difference in median PFS, a subset of patients experienced a more significant benefit with belzutifan, resulting in a notable divergence in the belzutifan curve and an HR significantly below 1, Rini explains.

Although an OS advantage with belzutifan has not yet been established, there is a disparity in median OS between the 2 arms, he expands, and further data maturation may shed light on potential OS benefits with belzutifan. Prolonged OS has historically been challenging to demonstrate in this refractory setting, Rini elucidates. Nonetheless, considering the favorable tolerability profile, PFS data, and partial quality of life data with belzutifan, this agent represents a promising addition to the RCC treatment armamentarium, he emphasizes. Additionally, addressing remaining unmet needs in refractory kidney cancer, particularly with the development of efficacious drugs, remains crucial, Rini concludes.