FDA Approves Belzutifan Plus Lenvatinib for PD-1/PD-L1-Refractory Advanced Clear Cell RCC
核心洞察
The FDA approved belzutifan in combination with lenvatinib for adults with advanced clear cell renal cell carcinoma (搜索) whose disease progressed on a PD-1 (搜索) or PD-L1 (搜索) inhibitor.
The phase 3 LITESPARK-011 trial showed median progression-free survival of 14.6 months with the combination versus 10.6 months with cabozantinib, with a hazard ratio of 0.74.
Overall survival was 33.7 months with belzutifan plus lenvatinib versus 28.6 months with cabozantinib, and objective response rates were 53% versus 40%.
The FDA has approved belzutifan (Welireg) in combination with lenvatinib (Lenvima) for adult patients with advanced clear cell renal cell carcinoma (搜索) (ccRCC) whose disease has progressed following treatment with a PD-1 (搜索) or PD-L1 (搜索) inhibitor, according to an agency news release.
The approval covers a patient group that has limited options after checkpoint inhibitor therapy fails, and it is supported by randomized phase 3 data comparing the combination against an established oral multikinase inhibitor.
LITESPARK-011 Results
The supporting evidence comes from the phase 3 LITESPARK-011 trial (NCT04586231), which evaluated the investigational combination against cabozantinib (Cabometyx) in patients with locally advanced or metastatic ccRCC.
Median progression-free survival (PFS) by blinded independent central review was 14.6 months (95% CI, 11.1-16.6) with belzutifan plus lenvatinib versus 10.6 months (95% CI, 9.2-11.1) with cabozantinib. The hazard ratio for PFS was 0.74 (95% CI, 0.61-0.89; P = 0.00095).
A final analysis of overall survival (OS) showed 33.7 months (95% CI, 29.0-46.9) in the belzutifan/lenvatinib arm versus 28.6 months (95% CI, 24.1-31.4) in the cabozantinib arm, with a hazard ratio of 0.85 (95% CI, 0.70-1.03).
Objective response rate (ORR) was 53% (95% CI, 47%-58%) with the combination compared with 40% (95% CI, 35%-45%) with cabozantinib (P = 0.0002).
Dosing and Safety
The recommended dosage is 20 mg of lenvatinib and 120 mg of belzutifan taken once daily until disease progression or unacceptable toxicity.
The prescribing information for belzutifan includes boxed warnings for embryo-fetal toxicity, along with warnings and precautions for anemia and hypoxia. Lenvatinib's prescribing information carries warnings and precautions for hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, among other conditions. Taken together, the combination includes warnings and precautions for cardiac dysfunction.