Pembrolizumab was a safe and effective adjuvant treatment for stage 2B or 2C melanoma, according to results from the first and second interim analyses of a double-blind, randomized, placebo-controlled multinational phase 3 study published in the Lancet.
Investigators recruited patients aged 12 years or older with completely resected stage 2B or 2C melanoma and randomly assigned them 1:1 to receive either intravenous pembrolizumab 200 mg, an anti-PD-1 monoclonal antibody, or placebo every 3 weeks. Treatment lasted for 17 cycles or until disease recurrence or unacceptable toxicity occurred. The primary endpoint was recurrence-free survival in the intention-to-treat population, which was met if recurrence-free survival was significantly improved for the pembrolizumab group compared with the placebo group at either the first or second interim analysis. Patients with a diagnosis of new primary melanoma were discontinued from the study. Investigators also assessed safety in all patients who received at least 1 dose of pembrolizumab via patient or caregiver self-reported data.
Of the 976 patients included in the study, the mean age was 61 years (IQR, 52-69), 60% were men, 90% were White, and 82% were not Hispanic or Latino. There were 2 pediatric patients (12-18 years of age) included in the study, 1 in each treatment group.
At the first interim analysis, which took place after a median 14.4 months of follow-up (IQR, 10.2–18.7 months) in the pembrolizumab group and 14.3 months (IQR, 10.1 – 18.7 months) in the placebo group, 11% of patients treated with pembrolizumab had a first recurrence of disease or died compared with 17% of patients treated with placebo (hazard ratio [HR], 0.65; 95% CI, 0.46–0.92; P =.0066). At the second interim analysis which occurred after a median 20.9 months of follow-up in both groups, 15% of patients treated with pembrolizumab had a first recurrence of disease or died compared to 24% of patients treated with placebo (HR, 0.61; 95% CI, 0.45–0.82). The estimated 18-month recurrence-free survival rate was 86% for pembrolizumab and 77% for placebo.
At the first interim analysis, treatment-related adverse events of any grade occurred in 80% of patients in the pembrolizumab group and 61% of patients in the placebo group. Grade 3-4 treatment-related adverse events occurred in 16% of the pembrolizumab group compared to 4% of the placebo group. There were no treatment-related deaths.
The study was limited by the small number of pediatric patients.
The study authors reported that based on the data from this trial, the FDA recently approved pembrolizumab as an adjuvant therapy for adult and pediatric patients with high-risk stage 2 and stage 3 melanoma.
Disclosure: This research was supported by Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA. Please see the original reference for a full list of disclosures.
Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718-1729. doi:10.1016/S0140-6736(22)00562-1