CHICAGO — Final analysis of data from the phase 3 KEYNOTE-006 presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting confirm the superiority of pembrolizumab over ipilimumab for advanced melanoma.1

At a median follow-up of 23 months, the median overall survival for pembrolizumab was not reached, reported Jacob Schachter, MD, Ella Institute for Research and Treatment of Melanoma, Sheba Medical Center, Ramat-Gan, Israel.

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At 24 months, approximately 30% of pembrolizumab-treated patients were alive and progression free, and “responses to pembrolizumab, including complete response, continued to accrue and were as durable as responses to ipilimumab,” he said.

Previous results demonstrated that the anti-PD-1 agent provided superior overall survival and progression-free survival and a lower incidence of grade 3-5 treatment-related adverse events vs ipilimumab in patients with advanced melanoma who had received 1 or fewer prior therapies.

The KEYNOTE-006 study randomly assigned 834 patients to 24 months of pembrolizumab 10 mg/kg every 3 weeks (n = 279) or every 2 weeks (n = 277) or to ipilimumab 3 mg/kg every 3 weeks for 4 doses (n = 278).

Patients who were stable clinically with radiologic progression could receive treatment until confirmed progression.

The final analysis showed that pembrolizumab continued to provide superior overall survival, progression-free survival, and overall response rates compared with ipilimumab, with no difference between the pembrolizumab schedules.

At 24 months, median overall survival was not reached for pembrolizumab every 2 weeks (95% CI, 22.1-NR) or every 3 weeks (95% CI, 23.5-NR) compared with 16.0 months (95% CI, 13.5-22.0) with ipilimumab; estimated 24-month rates were 55% (HR, 0.68; 0.53-0.87; P = .0008) for pembrolizumab every 2 weeks; 55% (HR, 0.68; 95% CI, 0.53-0.86; P = .0008) for pembrolizumab every 3 weeks; and 43.0% for ipilimumab.

Median progression-free survival was 5.6 months in the pembrolizumab every 2 weeks arm, 4.1 months in the every 3 weeks arm, and 2.8 months in the ipilimumab arm. The 24-month rate was 31% (HR, 0.61; 95% CI, 0.50-0.75; P < .00001), 28% (HR, 0.61; 95% CI, 0.50-0.75; P < .00001), and 14%, respectively.

Kaplan-Meier curves for progression-free survival appeared to flatten after approximately 20 months for all arms. Dr. Schachter said Kaplan-Meier estimates suggest that 70% of patients who respond have a response that lasts 72 weeks or longer.

Overall response rate was 37% in the pembrolizumab every 2 weeks arm, with complete response in 12%; for every 3 weeks it was 36% and 13%, and for ipilimumab, 13% and 5%, respectively.

One treatment-related death occurred, sepsis in the pembrolizumab every 2 weeks arm.

The safety profile was consistent with that previously reported, with 17% grade 3/4 treatment-related adverse events in both of the pembrolizumab arms and 20% in the ipilimumab arm, Dr. Schachter concluded.


1. Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: Final overall survival analysis of KEYNOTE-006. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.