On December 3, 2021, the FDA approved a new indication for the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for the adjuvant treatment of adult and pediatric patients (age ≥12 years) with stage IIB or IIC melanoma following complete resection. The FDA also expanded the indication for this agent as adjuvant treatment for stage III melanoma following complete resection to include pediatric patients.
The FDA approved this new indication for patients with stage IIB and IIC melanoma based on findings from the first interim analysis of the phase 3 KEYNOTE-716 trial of 976 patients with completely resected stage IIB or IIC melanoma. Patients were randomized to receive pembrolizumab 200 mg or the pediatric dose of 2 mg/kg intravenously (up to a maximum of 200 mg) every 3 weeks or placebo for up to 1 year until disease recurrence or unacceptable toxicity.
The main efficacy outcome measure for the trial was investigator-assessed recurrence-free survival. Results showed a statistically significant improvement in recurrence-free survival at the time of the first interim analysis for patients randomized to the pembrolizumab arm compared with those randomized to the placebo arm, with a hazard ratio of 0.65 (95% confidence interval, 0.46-0.92; P = .0132). The median recurrence-free survival was not reached in either arm.
Efficacy in pediatric patients aged ≥12 years, who have stage IIB, IIC, and III melanoma is supported by extrapolation of efficacy findings from adults, given similar biology, pharmacology, of drug effect, as well as similar exposure response for efficacy and safety.
The most common (≥20%) adverse reactions reported in the KEYNOTE-716 trial were fatigue, diarrhea, pruritus, and arthralgia.