• DOI:10.1056/NEJMoa1503093
• Corpus ID: 41000029

Pembrolizumab versus Ipilimumab in Advanced Melanoma.

@article{Robert2015PembrolizumabVI,
  title={Pembrolizumab versus Ipilimumab in Advanced Melanoma.},
  author={Caroline Robert and Jacob Schachter and Georgina V. Long and Ana M Arance and Jean Jacques Grob and Laurent Mortier and Adil I. Daud and Matteo S Carlino and Catriona M. McNeil and Michal Lotem and James M. G. Larkin and Paul C. Lorigan and Bart Neyns and Christian U. Blank and Omid Hamid and Christine Mateus and Ronnie Shapira-Frommer and Michele Kosh and Honghong Zhou and Nageatte Ibrahim and Scot W. Ebbinghaus and Antoni Ribas},
  journal={The New England journal of medicine},
  year={2015},
  volume={372 26},
  pages={
          2521-32
        }
}

• C. Robert, J. Schachter, +19 authors A. Ribas
• Published 24 June 2015
• Medicine
• The New England journal of medicine

BACKGROUND
The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma.

METHODS
In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progression-free and overall survival.

RESULTS
The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P=0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P=0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%).

CONCLUSIONS
The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials.gov number, NCT01866319.).