Neoadjuvant–adjuvant bests adjuvant-only pembrolizumab in advanced melanoma

For patients with stage III or IV melanoma, treatment with pembrolizumab both before and after surgical resection leads to longer event-free survival than treatment with pembrolizumab only after the procedure, according to the results of a phase II study.

The study included 313 patients with clinically detectable, measurable stage IIIB to IVC melanoma who were scheduled for surgical resection. These patients were randomly assigned to receive three doses of neoadjuvant pembrolizumab and then 15 doses of adjuvant pembrolizumab (neoadjuvant–adjuvant group, n=154) or to adjuvant pembrolizumab alone (200 mg intravenously every 3 weeks for a total of 18 doses; adjuvant-only group, n=159).

The primary outcome was event-free survival in the intention-to-treat population. Events were characterized as follows: disease progression or toxic effects that prohibited resection; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after resection; recurrence of melanoma after surgery; or death from any cause. Safety was also assessed.

Over a median follow-up of 14.7 months, event-free survival was significantly longer in the neoadjuvant–adjuvant group than in the adjuvant-only group (p=0.004). A landmark analysis showed that 72 percent (95 percent confidence interval [CI], 64–80) of patients in the neoadjuvant–adjuvant group were event-free at 2 years as compared with 49 percent (95 percent CI, 41–59) in the adjuvant-only group.

Treatment-related adverse events of grades 3 or higher during therapy occurred in 12 percent of patients in the neoadjuvant–adjuvant group and in 14 percent in the adjuvant-only group.