At a 3-years median follow-up, the randomized, phase 3 EORTC 1325/KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab taken for up to 1 year in high-risk stage III melanoma patients improved recurrence-free survival (RFS), with a consistent effect across subgroups.
Prof. Alexander Eggermont (Princess Máxima Centre for Paediatric Oncology, the Netherlands) presented the study , whose purpose was to assess whether post-surgery therapy with pembrolizumab improves disease recurrence for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB, and IIIC), as compared with placebo.
The EORTC 1325/KEYNOTE-054 trial included 1,019 adults with stage IIIA (15%), stage IIIB (46%), or stage IIIC (39%) resected melanoma metastatic to lymph nodes. Patients were assigned to either adjuvant pembrolizumab (200 mg every 3 weeks) for up to 1 year (n=514) or placebo (n=505) for a total of 18 doses, until disease recurrence or unacceptable toxicity. The co-primary endpoints were RFS in the intent-to-treat population as a whole, and in patients with PD-L1-positive tumors as a pre-specified subgroup analysis.
Previously, with a median follow-up of 1.25 years, the investigators reported improved RFS for pembrolizumab compared with placebo (HR 0.57). In the current presentation, results with a median follow-up of 3.05 years again showed superior RFS for the pembrolizumab group compared with the placebo group (190 vs 283 RFS events; HR 0.56; 95% CI 0.47-0.68). Among patients with PD-L1-positive tumours (n=853), 3-year RFS rates with pembrolizumab were also better than placebo (65% vs 46%; HR 0.57; 95% CI 0.43-0.74; P<0.001). Pembrolizumab was also better for the RFS of patients with BRAF-mutated tumours (n=440; 62% vs 37%; HR 0.51; 95% CI 0.36-0.73) and patients with BRAF wild-type tumours (n=448; 62% vs 47%; HR 0.66; 95% CI 0.46-0.95).
In conclusion, adjuvant pembrolizumab conferred a durable, clinically meaningful RFS benefit for patients with resected high-risk stage III melanoma. “We have shown that longer follow-up confirms a very sustained RFS benefit for pembrolizumab compared with placebo,” Prof. Eggermont said. Elaborating on the road ahead for this study, he added: “We will report on distant metastasis-free survival when they are ready in the next 6 or 7 months”.
1. Eggermont AM, et al. Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up. ASCO Virtual Meeting, 29-31 May 2020, Abstract 10000.