CHICAGO – Adjuvant pembrolizumab for resected high-risk melanoma slowed the rate of recurrence or death by 43% compared with placebo in a phase 3 trial of 1,519 patients.
After 15 months of follow-up, 12-month rates of recurrence-free survival (RFS) were 75% for pembrolizumab and 61% for placebo (hazard ratio, 0.57; P less than .001), Alexander M.M. Eggermont, MD, PhD, reported at the annual meeting of the American Association for Cancer Research.
By 18 months, the RFS difference between the arms had widened even more (71% versus 53%), Dr. Eggermont and his associates said at the meeting. The report was published simultaneously in the New England Journal of Medicine.
Adjuvant pembrolizumab was effective irrespective of PD-L1 tumor expression status. In a subgroup of more than 800 patients with PD-L1-positive tumors, 12-month RFS rates were 77% for pembrolizumab and 63% for placebo (HR, 0.54; 95% CI, 0.42 to 0.69; P less than .001). Among 116 patients who were PD-L1-negative, these rates were 72% and 52%, respectively (HR, 0.47; P = .01).
Treatment produced no new safety signals, said Dr. Eggermont of Gustave Roussy Cancer Campus Grand Paris and University Paris-Saclay, Villejuif, France. Grade 3 or higher toxicities affected 15% of pembrolizumab patients. Myositis caused one pembrolizumab-related death.
The findings bolster data suggesting that adjuvant therapy can stop or delay recurrence in resected high-risk melanoma. Previously, adjuvant ipilimumab was approved after significantly extending RFS and overall survival in the placebo-controlled European Organization for Research and Treatment of Cancer 18071 trial. More recently, adjuvant dabrafenib plus trametinib reduced the risk of recurrence compared with placebo in completely resected stage III melanoma with BRAF mutations (COMBI-AD), and adjuvant nivolumab significantly improved RFS and was less toxic than was ipilimumab in patients with advanced resected BRAF-mutated and BRAF-wild-type melanomas (CheckMate 238).