Advanced RCC: pembrolizumab-axitinib tops sunitinib in KEYNOTE-426

  • Rini BI & et al.
  • N Engl J Med
  • 16 Feb 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • 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.

Study design

  • 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.

Key results

  • 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.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.