On December 3, 2021, the FDA accelerated the approval of the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for the adjuvant treatment of patients aged ≥12 years with stage IIB or stage IIC melanoma, after complete resection. The FDA granted pembrolizumab an orphan drug designation for this indication. Pembrolizumab has been previously approved by the FDA for many oncologic indications.
The efficacy for this indication was evaluated in the KEYNOTE-716 study, a multicenter, randomized (1:1), double-blind, placebo-controlled clinical trial in patients with completely resected stage IIB or stage IIC melanoma. Patients were randomized to pembrolizumab 200 mg or to the intravenous pediatric dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks or to placebo for up to 1 year, until disease recurrence or unacceptable adverse events.
The primary end point was investigator-assessed recurrence-free survival (RFS). The first interim analysis demonstrated a significant improvement in RFS in patients who received pembrolizumab versus those who received a placebo (hazard ratio, 0.65; 95% confidence interval, 0.46-0.92; P = .0132). At the time of the analysis, the median RFS was not reached in either arm.
The most common (≥20%) adverse reactions reported with pembrolizumab in the KEYNOTE-716 study were fatigue, diarrhea, pruritus, and arthralgia.