On February 15, 2019, pembrolizumab (KEYTRUDA, Merck) was approved by the Food and Drug Administration for the adjuvant treatment of patients with melanoma with the involvement of lymph node(s) after full resection.
The approval was based on EORTC1325/KEYNOTE-054 (NCT02362594), a randomized, double-blind, placebo-controlled trial of 1019 completely resected, stage IIIA (>1 mm metastasis of the lymph node), IIIB or IIIC melanoma patients (AJCC 7th ed). Mucosal or ocular melanoma patients were not eligible. Patients were randomly assigned to receive pembrolizumab 200 mg every 3 weeks (1:1) or placebo for up to 1 year before recurrence of the disease or unacceptable toxicity. The registration required full resection of melanoma with negative margins, dissection of the lymph node and if indicated, completion of radiotherapy within 13 weeks prior to commencement of care.
As tested by researchers according to RECIST version 1.1, the primary efficacy outcome indicator was recurrence-free survival (RFS). RFS was described as the time between the randomization date and the first recurrence (local, regional, or distant metastasis) or any cause of death that occurred first. Fewer recurrences/deaths occurred in patients receiving pembrolizumab, 26 percent (n=135), compared to 43 percent (n=216) on the placebo arm (hazard ratio 0.57; 95 percent CI: 0.46, 0.70; p<0.001). Regardless of tumor PD-L1 expression, the RFS value of pembrolizumab relative to placebo was observed. In the placebo arm, the median RFS was 20.4 months and was not attained for those receiving pembrolizumab.
Seventy-six percent of patients received 6 months or longer of pembrolizumab. Pembrolizumab was discontinued in 14 percent of patients because of adverse reactions. The most common adverse reactions (reported in at least 10% of pembrolizumab-treated patients) were diarrhea, pruritus, nausea, arthralgia, hypothyroidism, cough, rash, asthenia, influenza-like illness, weight loss, and hyperthyroidism.
The recommended pembrolizumab dose and schedule for the adjuvant treatment of melanoma is 200 mg administered as an IV infusion over 30 minutes every 3 weeks until disease recurrence or unacceptable toxicity, for a maximum of 1 year.
FDA granted this application standard review and Orphan Designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.