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
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Takeaway

  • 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.

Limitations

  • Short follow-up.

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