- Pembrolizumab plus axitinib improves OS, PFS, and overall response rate (ORR) in treatment-naive patients with advanced renal cell carcinoma (RCC) vs sunitinib.
- Survival benefit was observed in intermediate/poor-risk and programmed death ligand-1 (PD-L-1)-positive patients.
Why this matters
- The FDA has granted priority review to first-line pembrolizumab+axitinib, based on these findings.
- KEYNOTE-426: open-label, phase 3 trial of 861 treatment-naive patients with advanced clear-cell RCC, randomly assigned to pembrolizumab+axitinib or sunitinib.
- Funding: MSD.
- Median follow-up, 12.8 months.
- Pembrolizumab+axitinib significantly improved 12-month OS vs sunitinib (89.9% vs 78.3%; HR, 0.53; P<.0001>
- Median PFS was significantly longer with pembrolizumab+axitinib (15.1 vs 11.1 months; HR, 0.69; P<.001>
- Pembrolizumab+axitinib significantly improved ORR (59.3% vs 35.7%; P<.001>
- OS and PFS benefit was observed in patients with:
- intermediate risk: HR, 0.53 (95% CI, 0.35-0.82) and 0.70 (95% CI, 0.54-0.91), respectively;
- poor risk: HR, 0.43 (95% CI, 0.23-0.81) and 0.58 (95% CI, 0.35-0.94), respectively; and
- combined PD-L-1 score ≥1: HR, 0.54 (95% CI, 0.35-0.84) and 0.62 (95% CI, 0.47-0.80), respectively.
- Grade ≥3 adverse event rate was higher with pembrolizumab+axitinib (75.8% vs 70.6%).
- Hepatic events were more frequent with pembolizumab+axitinib.
- Hematologic toxicities were more common with sunitinib.
- Short follow-up.