The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency (EMA), has recommended the approval of Keytruda (pembrolizumab) for the treatment of advanced melanoma patients whose tumor has been completely removed in surgery.
The European Commission will now review CHMP’s opinion before making a final decision regarding approval, which is expected by year’s end.
“There is a growing need for innovative therapies that can help reduce the risk of recurrence following surgery in patients with stage III melanoma,” Scot Ebbinghaus, MD, vice president of clinical research for Merck Research Laboratories, said in a press release. “Today’s news reflects the collaborative efforts of Merck and the European Organisation for Research and Treatment of Cancer (EORTC) to improve the way we treat melanoma earlier in the treatment paradigm.
“We look forward to working with European regulatory authorities to bring Keytruda to these patients in the adjuvant setting.”
The recommendation was based on clinical evidence from the pivotal KEYNOTE-054 Phase 3 trial (NCT02362594), in which Keytruda significantly extended the time patients lived without their cancer returning over a placebo.
Conducted by Merck (known as MSD outside the United States and Canada) in collaboration with the EORTC, the trial included 1,019 adults with stage 3 melanoma — cancer that has spread to the lymph nodes — who had undergone a complete surgical removal of their tumor.
The trial was aimed at determining if Keytruda could delay the tumor from returning — a measure called recurrence-free survival — both in the overall population and in patients whose tumors were positive for the PD-L1 molecule — which usually predicts responses to Keytruda.
In the trial, more patients receiving Keytruda lived one year or more without their disease returning (75.4%) compared with those on placebo (61%), representing a 43% reduction in the risk of disease recurrence or death.
At 18 months, the differences were even more striking, with 71.4% of Keytruda-treated patients living 18 months or more without disease recurrence compared with 53.2% of patients receiving a placebo.
Similar results were seen in the 853 patients whose tumors produced PD-L1. In this subgroup, Keytruda led to a 12-month recurrence-free survival of 77.1% versus 62.6% for placebo. Overall, PD-L1-positive patients on Keytruda were 46% less likely to experience disease recurrence or death.
“As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence-free survival than placebo, with no new toxic effects identified,” the researchers wrote.
In KEYNOTE-054, serious and life-threatening adverse events were more common in the Keytruda group — 14.3% vs. 3.4%. One patient died due to Keytruda treatment, which caused a severe muscle inflammation.