In a study published in the Journal of Clinical Oncology, pembrolizumab adjuvant therapy was found to provide a “sustained and clinically meaningful” improvement in recurrence-free survival (RFS) at 3-year median follow-up in patients with resected high-risk stage III melanoma (2020. doi:10.1200/JCO.20.02110).
Researchers had conducted the phase 3, double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients with resected high-risk stage III melanoma. Pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo at a 1.25-year median follow-up on the basis of 351 RFS events. These findings led the European Medicines Agency and Food and Drug Administration to approve pembrolizumab adjuvant treatment.
In the present study, authors Alexander MM Eggermont, MD, PhD, Princess Máxima Center, Utrecht, the Netherlands, and colleagues report an updated RFS analysis at the 3.05-year median follow-up. Patients were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity.
A total of 1019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were included. The study’s two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)-positive tumors.
Authors founds that pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% vs 44.1% for pembrolizumab vs placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1-positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74).
In addition, the impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] vs 0.66 [99% CI, 0.46 to 0.95] for V600E/K vs wild type).
Dr Eggermont and coauthors concluded that, in patients with resected high-risk stage III melanoma at 3-year median follow-up, pembrolizumab adjuvant therapy provided meaningful improvement in RFS. Improvement was also consistent across subgroups.—Amanda Del Signore