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.).