Belzutifan Versus Everolimus for Previously Treated, Advanced Clear Cell RCC

Updated data presented as a late-breaking abstract at the European Society for Medical Oncology Congress 2023 showed belzutifan is associated with a statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) versus everolimus for patients with advanced clear cell renal cell carcinoma (ccRCC) after previous immune checkpoint and anti-angiogenic therapies.

Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Institute, presented the latest results of the LITESPARK-005 study.

A total of 374 patients aged at least 18 years with a Karnofsky Performance Status of at least 70% were included in the study. Patients must have received 1 to 3 prior systemic regimens, including at least 1 anti-PD-L1 agent and at least 1 VEGF-TKI. Patients were randomized (1:1) to receive belzutifan or everolimus until disease progression or unacceptable toxicity.

The dual primary end points were PFS per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and overall survival (OS). Among the secondary end points were ORR per RECIST version 1.1 and safety.

At the first interim analysis, PFS and ORR were formally tested. After a median follow-up of 18.4 months, patients in the belzutifan arm benefited from statistically significant increases in PFS and ORR. Dr. Albiges shared that 22.5% of patients in the belzutifan arm were progression-free compared with 9.0% of patients in the everolimus arm (hazard ratio, 0.74; 95% CI, 0.63-0.88). The ORR was 22.7% versus 3.5%, respectively, and a complete response was observed in 3.5% of belzutifan patients versus none in the everolimus arm.

No overall survival benefits have been observed for belzutifan in the study. While OS rates of 55.2% and 50.6%, respectively, were reported, statistical significance has not been met.

At the second interim analysis (median follow-up, 25.7 months), PFS, OS, and ORR results were consistent with those of the first interim analysis.

Dr. Albiges noted that the safety profile of belzutifan was consistent with prior reports, and no new safety signals were observed.

In her concluding remarks, she said LITESPARK-005 is the first positive phase 3 study in patients with advanced kidney cancer following immune checkpoint and anti-angiogenic therapies, adding that belzutifan continues to be explored in other phase 3 neoadjuvant and adjuvant settings.