Real-World Efficacy and Safety of Belzutifan in Sporadic Metastatic Renal Cell Carcinoma.

INTRODUCTION: Belzutifan, a HIF-2α inhibitor, is approved for von Hippel-Lindau (VHL)-tumors and sporadic metastatic renal cell carcinoma (mRCC) after prior immunotherapy (IO) and tyrosine kinase inhibitor (TKI) therapy. Real-world data on outcomes and adverse events (AEs) of belzutifan in patients not represented in clinical trial settings remain limited. PATIENTS AND METHODS: A multicenter retrospective study of patients with mRCC treated with belzutifan was performed. Clinical efficacy outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Treatment-related AEs were also recorded. RESULTS: A total of 43 patients received belzutifan (26% Hispanic). Median age was 67 years (range, 21-86). Clear cell histology was predominant (91%); other histologies included mixed clear cell/papillary (n = 1); chromophobe with somatic VHL alteration (n = 1); unclassified RCC (n = 1). Common sites of metastases at belzutifan start included liver (33%), bone (30%), and peritoneum (19%). The median number of prior therapies was 3 (range, 0-6) including prior IO (95%) and TKI (88%). Among 36 evaluable patients, ORR was 25% (9 partial responses). At a median follow-up of 8.2 months, the median PFS was 5.7 months (95% CI, 3.3-10.7) and median OS was not reached (95% CI, 12.0-NR). Any AE was reported in 93% with all-grade anemia (79%), fatigue (30%); hypoxia (14%) being most common. The most frequent grade 3 to 5 AEs were anemia (30%) and hypoxia (7%). Discontinuation due to AE occurred in 12%. CONCLUSIONS: In this diverse, heavily pre-treated mRCC cohort with frequent visceral metastases, belzutifan had consistent clinical outcomes and toxicity profile with prior reports.