Adjuvant Pembrolizumab versus IFNα2b or Ipilimumab in Resected High-Risk Melanoma

Cancer Discov. 2022 Mar 1;12(3):644-653. doi: 10.1158/2159-8290.CD-21-1141.


We conducted a randomized phase III trial to evaluate whether adjuvant pembrolizumab for one year (647 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison with high-dose IFNα-2b for one year or ipilimumab for up to three years (654 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies [HR, 0.77; 99.62% confidence interval (CI), 0.59-0.99; P = 0.002]. There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI, 0.61-1.09; P = 0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with IFNα-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared with the prior standard-of-care immunotherapies for patients with high-risk resected melanoma.

Significance: Adjuvant PD-1 blockade therapy decreases the rates of recurrence, but not survival, in patients with surgically resectable melanoma, substituting the prior standard-of-care immunotherapies for this cancer. See related commentary by Smithy and Shoushtari, p. 599. This article is highlighted in the In This Issue feature, p. 587.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antineoplastic Agents, Immunological / adverse effects
  • Humans
  • Ipilimumab* / adverse effects
  • Melanoma* / drug therapy
  • Melanoma* / surgery
  • Risk Assessment


  • Adjuvants, Immunologic
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Ipilimumab
  • pembrolizumab