Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial
Summary. In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. The durability of these benefits with a median follow-up of 3.5 and 5 years had been published earlier. This study presents results with a longer follow-up period. Materials and methods. A total of 1019 patients were randomized to receive pembrolizumab at a dose of 200 mg or placebo intravenously every 3 weeks (for a total of 18 doses). The primary endpoints were RFS in the overall population and in the subgroup of PD-L1-positive melanoma patients. The secondary endpoint was DMFS in these two populations, and the exploratory endpoint was progression / recurrence-free survival 2 (PFS2). Results. The median follow-up was 6.9 years. In the overall population of treated patients, RFS was longer in the pembrolizumab group than in the placebo group (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.53–0.74). At 7 years, RFS was 50% (95% CI 46–55%) in the pembrolizumab group and 36% (95% CI 32–41%) in the placebo group. Positive effects of pembrolizumab treatment were observed in both loco-regional recurrences and distant metastases, as well as in IIIA–C melanoma substages, PD-L1-positive and PD-L1-negative populations, and in both BRAF mutation-positive patients and those without BRAF mutations. DMFS was longer in the pembrolizumab group than in the placebo group (HR 0.64, 95% CI 0.54–0.76). DMFS at 7 years was 54% (95% CI 50–59%) in the pembrolizumab group and 42% (95% CI 37–46%) in the placebo group. PFS2 was longer in the pembrolizumab group than in the placebo group (HR 0.69, 95% CI 0.57–0.84). PFS2 at 7 years was 61% (95% CI 57–66%) in the pembrolizumab group and 53% (95% CI 49–57%) in the placebo group. Conclusions. The seven-year analysis of pembrolizumab’s efficacy in the adjuvant setting demonstrated sustained improvements in long-term RFS, DMFS, and PFS2 compared to placebo in patients with resected stage III melanoma.
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