Pembrolizumab has been shown to improve 6-month progression-free survival for patients with ipilimumab-refractory melanoma, according to a study published online ahead of print in The Lancet Oncology.

In a phase 2 trial, 540 patients were randomly assigned to receive either intravenous pembrolizumab 2 mg/kg every 3 weeks (n=180), 10 mg/kg every 3 weeks (n=181), or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide; n=179).

Randomization was stratified by ECOG PS, lactate dehydrogenase concentration, and BRAFV600 mutation status. Eligibility criteria included patients with confirmed progressive disease within 24 weeks after two or more ipilimumab doses, and, if BRAFV600 mutant positive, received previous treatment with a BRAF, MEK inhibitor, or both; resolution of all ipilimumab-related adverse events (grade 0-1); prednisone 10 mg/day or less for at least 2 weeks; an ECOG PS of 0 or 1; and at least one measurable lesion.

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Findings from the primary endpoint at the prespecified second interim analysis of progression-free survival (PFS) in the intention-to-treat population showed improvement in the pembrolizumab 2 mg/kg group (HR = 0.57, 95% CI: 0.45-0.73;P<0.0001) and the 10 mg/kg group (HR = 0.50, 95% CI: 0.39-0.64; P<0.0001) compared with the chemotherapy group.

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Patients in the pembrolizumab 2 mg/kg group had a 6-month PFS rate of 34%; the pembrolizumab 10 mg/kg group had 38%; and the chemotherapy group had 16%.

Grade 3-4 treatment-related adverse events (TRAEs) occurred in 11% of patients in the 2 mg/kg group, 14% in the 10 mg/kg group, and 26% in the chemotherapy group. The most common grade 3-4 TRAE was fatigue in the pembrolizumab groups (1% in the 2 mg/kg group; <1% in the 10 mg/kg group, and 5% in the chemotherapy group).


  1. Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015. [epub ahead of print]. doi: 10.1016/S1470-2045(15)00083-2.