ASCO-GU 2019—Pembrolizumab+axitinib better than sunitinib in advanced or metastatic clear-cell RCC

  • Melissa Pandika
  • Univadis
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  • Pembrolizumab combined with axitinib showed longer OS and PFS, and a higher objective response rate (ORR) in patients with previously untreated, advanced or metastatic clear-cell renal cell carcinoma (mRCC).

Why this matters

  • mRCC has a 5-year survival rate of only 12%.
  • Few significant advances in treating mRCC have emerged.
  • New findings support first-line treatment with pembrolizumab+axitinib as a new standard of care in advanced or metastatic clear-cell RCC.

Study design

  • Phase 3 KEYNOTE-426 trial that randomly assigned 861 patients with clear-cell mRCC, no prior systemic therapy 1:1 to pembrolizumab (200 mg intravenously once every 3 weeks for up to 35 cycles) + axitinib (5 mg orally twice/day), or sunitinib (50 mg orally once/day for 4-weeks-on/2-weeks-off schedule) until progressive disease, intolerable toxicity, or patient/investigator decision.
  • Primary endpoints: OS, PFS.
  • Funding: MSD.

Key results

  • Median follow-up: 12.8 months.
  • OS rate at 12 months: 89.9% in pembrolizumab+axitinib arm, 78.3% in sunitinib arm (HR 0.53; P<.0001>
  • Median PFS: 15.1 months in pembrolizumab+axitinib arm, 11.1 months in sunitinib arm (HR 0.69; P=.0001).
  • ORR: 59.3% in pembrolizumab+axitinib arm, 35.7% in sunitinib arm.
  • Benefit of pembrolizumab+axitinib seen regardless of risk group, programmed death-ligand 1 status.


  • Median OS not yet reached.
  • Pembrolizumab+axitinib would likely require considerably more clinical visits than sunitinib.
  • Most patients worldwide do not and will not have access to this therapy.

Expert comment

  • It is exciting times. I think for the first-line metastatic renal cell patients with favorable-, intermediate-, and poor-risk disease, a checkpoint inhibitor/axitinib combination will be a new standard of care in many parts of the world, not all,” said Lori Wood, MD, associate professor in the Division of Medical Oncology at Dalhousie University, who was not involved in the trial.