The U.S. Food and Drug Administration (FDA) approved pembrolizumab for the initial treatment of patients with unresectable or metastatic melanoma.1

Pembrolizumab had received accelerated approval in 2014 for the treatment of patients with unresectable or metastatic melanoma who had experienced disease progression following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor.

Two new clinical trials formed the basis for the FDA to expand the indication of pembrolizumab. The first trial, which enrolled 540 patients who were refractory to prior ipilimumab and a BRAF inhibitor, if BRAF V600 mutation-positive, confirmed the clinical benefit of pembrolizumab in the previously approved setting.

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The study demonstrated a statistically significant improvement in progression-free survival in the pembrolizumab 2 mg/kg arm (HR, 0.57; 95% CI, 0.45 – 0.73; P < .001) and in the pembrolizumab 10 mg/kg arm (HR, 0.50; 95% CI, 0.39 – 0.64; P < .001) compared to investigator’s choice of chemotherapy. In terms of overall survival, there was no statistically significant difference between either pembrolizumab arm compared with the chemotherapy arm in the interim analysis. 

The second trial, which enrolled 834 patients who had not received ipilimumab and who had received no more than 1 line of prior systemic therapy, verified the benefit of pembrolizumab in the initial treatment setting.

Pembrolizumab 10 mg/kg every 2 weeks and every 3 weeks were associated with significant improvements in overall survival compared with ipilimumab (HR, 0.64; 95% CI, 0.47 – 0.83; P < .001 and HR, 0.69; 95% CI, 0.52-0.90; P = .004, respectively). There were also significant improvements in progression-free survival between the pembrolizumab arms and ipilimumab.

In regard to safety, the most common adverse events associated with pembrolizumab in the 2 studies were fatigue, pruritus, rash, constipation, nausea, diarrhea, and decreased appetite.

Pembrolizumab should be administered at a dose of 2 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.


  1. Pembrolizumab label updated with new clinical trial information [news release]. Silver Springg, MD: U.S. Food and Drug Administration. December 18, 2015. Accessed December 22, 2015.