A 1-year course of pembrolizumab spread out over 18 doses significantly reduced the risk of recurrence over placebo among patients with stage III melanoma who were deemed to be at high risk for recurrence following surgery, according to a new study presented at the American Association for Cancer Research (AACR) Annual Meeting, held from April 14–18 in Chicago.
“We hope that these data will lead to regulators in the United States and Europe approving pembrolizumab as a new treatment option for these patients,” Alexander M.M. Eggermont, MD, PhD, of the Gustave Roussy Cancer Campus in Villejuif, France, said in a press release. At the AACR meeting, Eggermont presented results of the KEYNOTE-045/EORTC 1325-MG trial.
The large phase III study included a total of 1,019 patients with completely resected stage III melanoma. They were randomized to receive either 200 mg pembrolizumab (n = 514) every 3 weeks for 1 year (total of 18 doses), or to placebo (n = 505). The results of the trial were published simultaneously in the New England Journal of Medicine.
After a median follow-up of 1.25 years, there were a total of 135 deaths (26.2%) in the pembrolizumab group, compared with 216 deaths (42.7%) in the placebo group. The 12-month RFS rate was 75.4% with the study drug and 61.0% with placebo, for a hazard ratio (HR) of 0.57 (98.4% CI, 0.43–0.74; P < .0001).
In the subgroup of 853 patients with programmed death ligand 1 (PD-L1)-positive tumors, the 1-year RFS rate was 77.1% with pembrolizumab and 62.6% in the placebo group (HR, 0.54; (95% CI, 0.42–0.69; P < .001). The total numbers were smaller, but the same was true in PD-L1–negative patients, favoring pembrolizumab (HR, 0.47; 95% CI, 0.26–0.85; P = .01).
Adverse events (AEs) of any grade deemed to be related to the trial regimen occurred in 77.8% of pembrolizumab-treated patients and in 66.1% of the patients who were randomized to placebo. AEs of grades 3, 4, or 5 that were related to the regimen were reported in 14.7% of patients in the pembrolizumab group and 3.4% of patients in the placebo group. One patient receiving pembrolizumab died due to myositis.
“An important aspect of this trial is that patients randomized to placebo who have recurrence are offered access to pembrolizumab,” Eggermont said. He noted that this cross-over design is unique among trials of adjuvant therapies for melanoma, and “will permit us to analyze if adjuvant therapy with pembrolizumab right after surgery is better or not than treating only those who relapse and start treatment at relapse.” It remains to be seen whether the RFS benefit will translate into an overall survival benefit with pembrolizumab in this setting.