The efficacy and safety of belzutifan inhibitor in patients with advanced or metastatic clear cell renal cell carcinoma: a meta-analysis

The belzutifan is a hypoxia inducible factor-2 alpha (HIF-2α) inhibitor for the treatment of advanced or metastatic clear cell renal cell carcinoma (mccRCC) and has exhibited good safety and efficacy in clinical trials. We conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of belzutifan for the treatment of mccRCC.

Multiple databases and abstracts from major scientific meetings were systematically reviewed for eligible articles published before June 1, 2024. The following outcomes were analyzed: objective response rate (ORR), disease control rate (DCR), median duration of response (mDOR), median progression-free survival (mPFS), median overall survival (mOS), and treatment-related adverse events (TRAes). 426 records were reviewed, and data were extracted by at least two individuals.

Seven studies involving 715 patients were included in this meta-analysis. The pooled ORR was 34% (95% confidence interval [CI]: 23–46%), the DCR was 79% (95% CI: 66–90%), the mDOR was 21.8 months (95% CI: 14.82–28.78), and the mPFS time was 8.8 months (95% CI: 6.15–11.44). The pooled incidence of grade 3–5 TRAes was 46%, and the most common TRAe was anemia. Further subgroup analysis revealed that, compared with belzutifan monotherapy, the combination of belzutifan with tyrosine kinase inhibitors (TKIs) as second- or later-line therapy was associated with a statistically significant increase in the ORR. Toxicity was also greater with combined inhibition therapy.

Our meta-analysis revealed moderate antitumor activity and a manageable safety profile of the inhibitor belzutifan in patients with mccRCC.