Pembrolizumab versus Ipilimumab in Advanced Melanoma

April 23, 2015

Abstract

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.

Source:

Robert, C, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. New England Journal of Medicine. April 19, 2015
DOI: 10.1056/NEJMoa1503093 http://www.nejm.org/doi/full/10.1056/NEJMoa1503093

Related information and sources:

The Australian Therapeutic Goods Administration (TGA) has registered pembrolizumab (trade name KEYTRUDA®) for the treatment of advanced metastatic melanoma. Australia is the first country in the world to register the drug for the first line treatment of unresectable or metastatic melanoma in adults.
http://www.melanoma.org.au/news-events/news/anti-pd1-immunotherapy-pembrolizumab-keytruda-has-been-registered-by-the-tga/

Melanoma Institute Australia and its key affiliate, Crown Princess Mary Cancer Centre Westmead were the highest recruiting centre worldwide for the study into the immunotherapies pembrolizumab versus ipilimumab, in advanced melanoma.
http://www.melanoma.org.au/news-events/news/mia-leads-the-world-first-study-that-finds-anti-pd-1-antibody-pembrolizumab-increases-the-survival-of-patients/