In the phase II SWOG Cancer Re­search Network S1801 trial reported in The New England Journal of Medicine, Sapna P. Patel, MD, and colleagues found that neoadjuvant plus adjuvant pembrolizumab significantly improved event-free survival vs adjuvant pembrolizumab alone in patients with stage IIIB to IV melanoma.

Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified.

— Sapna P. Patel, MD, and colleagues

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Study Details

The U.S. multicenter open-label trial included 313 patients with resectable stage III or oligometastatic resectable stage IV (M1a, M1b, and M1c) melanoma. Patients were randomly assigned between February 2019 and May 2022 to receive neoadjuvant pembrolizumab at 200 mg every 3 weeks for 3 doses and adjuvant pembrolizumab at 200 mg every 3 weeks for 15 doses (n =154) or adjuvant pembrolizumab at 200 mg every 3 weeks for 18 doses (n = 159).

The interval from the last dose of neoadjuvant pem­brolizumab to surgery was expected to be 5 weeks or less. Postoperative radiotherapy was permitted at investigator discretion before start of adjuvant therapy; concomitant administration of radiotherapy and pembrolizumab was not allowed. The primary endpoint was event-free survival in the intent-to-treat population.

Event-Free Survival

Median follow-up was 14.7 months. Event-free survival events occurred in 38 patients (25%) in the neoadjuvant-adjuvant group vs 67 (42%) in the adjuvant-only group. Event-free survival was significantly longer in the neoadjuvant-adjuvant group vs the adjuvant-only group (P = .004). In landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI] = 64%–80%) in the neoadjuvant-adjuvant group vs 49% (95% CI = 41%–59%) in the adjuvant-only group.

At data cutoff, death had occurred in 14 patients (9%) in the neoadjuvant-adjuvant group and 22 patients (14%) in the adjuvant-only group. The small number of events precluded definitive between-group comparison of overall survival.

Adverse Events

Treatment-related grade ≥ 3 adverse events occurred during neoadjuvant therapy in 7% of patients, most commonly increased alanine aminotransferase (ALT; n =3). During adjuvant therapy, treatment-related grade ≥ 3 adverse events occurred in 12% of patients in the neoadjuvant-adjuvant group and 14% of those in the adjuvant-only group; the most common were increased ALT and increased aspartate aminotransferase (AST; two patients each) in the neoadjuvant-adjuvant group and increased ALT, increased AST, and fatigue (two patients each) in the adjuvant-only group.   

The investigators concluded, “Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified.”

Dr. Patel, of The Uni­versity of Texas MD Anderson Cancer Center, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by the National Cancer Institute and Merck Sharp and Dohme. For full disclosures of the study authors, visit nejm.org.