Pembrolizumab vs Ipilimumab in Advanced Melanoma: Final Overall Survival Analysis of KEYNOTE-006

Key Points

  • In patients with unresectable stage III or IV melanoma, pembrolizumab (at 10 mg/kg every 2 weeks or every 3 weeks) prolonged overall survival vs ipilimumab.
  • Two-year survival was 55% in each pembrolizumab group vs 43% in the ipilimumab group.

The final overall survival analysis of the phase III KEYNOTE-006 trial showed maintained superiority of pembrolizumab (Keytruda) vs ipilimumab (Yervoy) in advanced melanoma. The results were reported by Schachter et al in The Lancet. An interim analysis showed improved progression-free and overall survival with pembrolizumab.

Study Details

In the open-label trial, 834 patients with unresectable stage III or IV melanoma (excluding ocular melanoma) and up to one previous systemic therapy (excluding anti–cytotoxic T-lymphocyte–associated protein 4 [CTLA-4], programmed cell death protein 1 [PD-1], or programmed cell death ligand 1 [PD-L1] agents) from 87 sites in 16 countries were randomized 1:1:1 between September 2013 and March 2014 to receive pembrolizumab at 10 mg/kg every 2 weeks (n = 279) or every 3 weeks (n = 277) or ipilimumab at 3 mg/kg every 3 weeks for 4 doses (n = 278). Patients with active brain metastases or active autoimmune disease requiring systemic steroids were excluded. The primary endpoint was overall survival in the intent-to-treat population.

Overall Survival

The final overall survival analysis occurred after all patients had been followed for at least 21 months; median follow-up was 22.9 months. Median overall survival was not reached in the pembrolizumab every-2-week group (hazard ratio [HR] vs ipilimumab = 0.68, P = .0009) or every-3-week group (HR vs ipilimumab = 0.68, P = .0008) and was 16.0 months in the ipilimumab group; no difference between the 2- vs 3-week pembrolizumab groups was observed (HR = 1.01; P = .93). Survival at 24 months was 55%, 55%, and 43%, respectively. Median progression-free survival was 5.6 months and 4.1 months vs 2.8 months (HR = 0.61, P < .0001, for both pembrolizumab groups vs ipilimumab).

The investigators concluded: “Substantiating the results of the interim analyses of KEYNOTE-006, pembrolizumab continued to provide superior overall survival versus ipilimumab, with no difference between pembrolizumab dosing schedules. These conclusions further support the use of pembrolizumab as a standard of care for advanced melanoma.”

Jacob Schachter, MD, of the Ella Lemelbaum Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel, is the corresponding author of The Lancet article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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