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The following is a summary of “Belzutifan Efficacy and Tolerability in Patients with Sporadic Metastatic Clear Cell Renal Cell Carcinoma,” published in the September 2024 issue of Urology by Wang et al.

Belzutifan, a hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor, was initially approved for the treatment of von Hippel-Lindau disease and, more recently, for sporadic metastatic clear cell renal cell carcinoma (ccRCC) based on the results of the LITESPARK-005 trial. Despite its growing significance, real-world data on the efficacy and safety of belzutifan in patients with sporadic, metastatic ccRCC remain scarce. This retrospective study seeks to describe the clinical outcomes of belzutifan in such patients, providing valuable insights into its performance outside of clinical trials.

A cohort of 22 patients with sporadic metastatic ccRCC, treated with belzutifan at MD Anderson Cancer Center before its Food and Drug Administration (FDA) approval, was evaluated. Key clinical endpoints included progression-free survival (PFS) and objective response rate (ORR), both assessed by a blinded radiologist according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median follow-up time was 14.9 months, with PFS and overall survival (OS) measured from the initiation of belzutifan therapy. Most patients had International Metastatic RCC Database Consortium intermediate-risk disease with more than three metastatic sites. It had undergone a median of five prior lines of therapy, including immune checkpoint inhibitors (ICT) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).

The results demonstrated meaningful clinical activity of belzutifan in this heavily pretreated population. The median PFS was 8.51 months (95% CI: 0–18.4 months), and the ORR was 36.4%. The median OS was 14.72 months (95% CI: 7.34–22.10 months). Despite its efficacy, adverse drug events (ADEs) were common, with anemia (77.3%) and hypoxia (36.4%) being the most frequently reported. About 4 patients (18.2%) required dose reductions, while three (13.6%) discontinued treatment due to ADEs. Notably, there were no treatment-related deaths.

In conclusion, this real-world analysis supports the use of belzutifan in patients with sporadic metastatic ccRCC, particularly after progression on ICT and VEGFR-TKIs. The observed clinical activity aligns with the findings of LITESPARK-005, reinforcing belzutifan’s role as a viable therapeutic option in this setting. These results also highlight the drug’s generally tolerable safety profile, though adverse effects such as anemia and hypoxia warrant careful monitoring in clinical practice.

Source: sciencedirect.com/science/article/abs/pii/S2405456924001755