Dr Rini on the FDA Approval of Belzutifan in Advanced RCC

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

On December 14th, 2023, the FDA approved belzutifan for patients with advanced RCC following progression on a PD-1 or PD-L1 inhibitor and a VEGF TKI. The agent's efficacy was assessed in the phase 3 LITESPARK-005 trial (NCT04195750), in which patients experienced a statistically significant improvement 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 vs 5.6 months (95% CI, 4.8-5.8) with everolimus. Although overall survival (OS) data are still immature, with 59% of deaths reported, there is no observed trend toward detriment with belzutifan. Additionally, a descriptive analysis of patient-reported symptom and functional outcomes favored belzutifan over everolimus.

Belzutifan is a HIF2α inhibitor with a novel mechanism of action, Rini begins. The therapeutic landscape in kidney cancer has primarily comprised of PD-1 inhibitors and multitargeted VEGF TKIs, he states. Although belzutifan's anti-angiogenic effect is related to the VEGF signaling pathway, it has several mechanistic differences compared with other RCC agents, Rini explains.

The FDA approval of belzutifan for patients with RCC holds significance because of the agent’s distinct biology andnotable tolerability, Rini continues, which set it apart from the standard TKIs employed in RCC management. The agent's favorable tolerability is particularly crucial in the refractory setting, where patients may have experienced challenges with other therapies, he notes.

Overall, the FDA approval of belzutifan for patients with advanced RCC provides clinicians with an alternative and potentially more well-tolerated option for patients in this population, especially in cases where traditional treatments may have limitations or are associated with adverse effects, Rini concludes.