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

BMC Pharmacol Toxicol. 2024 Dec 20;25(1):100. doi: 10.1186/s40360-024-00828-5.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

Keywords: Adverse events; Belzutifan; Clear cell renal cell carcinoma; Efficacy; Meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents