作者
Alexander M.M. Eggermont,Michal Kiciński,Christian U. Blank,Mario Mandalà,Georgina V. Long,Victoria Atkinson,Stéphane Dalle,Andrew Haydon,Andrey Meshcheryakov,Adnan Khattak,Matteo S. Carlino,Shahneen Sandhu,James Larkin,Susana Puig,Paolo A. Ascierto,Piotr Rutkowski,Dirk Schadendorf,Marye J. Boers‐Sonderen,Anna Maria Di Giacomo,Alfonsus Johannes Maria van den Eertwegh,Jean‐Jacques Grob,Ralf Gutzmer,Rahima Jamal,Alexander C. J. van Akkooi,Paul Lorigan,Dmitri Grebennik,Clemens Krepler,Sandrine Marréaud,Stefan Suciu,Caroline Robert
摘要
BackgroundIn the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence- and distant metastasis-free survival than placebo in patients with resected high-risk stage III melanoma. To confirm the stability of these benefits, longer-term data were needed.MethodsWe randomly assigned 1019 patients to receive 200 mg of pembrolizumab or placebo intravenously every 3 weeks for a total of 18 doses (approximately 1 year) and had previously reported data with a 15-, 36-, and 42-month median follow-up. We now report data at a median follow-up of 4.9 years. We report a number of outcomes, including recurrence-free survival in the overall population and in the subgroup of patients with cancer who were positive for the programmed death-ligand 1 (PD-L1). Distant metastasis-free survival was a secondary end point.ResultsIn the overall intention-to-treat population, pembrolizumab was still associated with longer recurrence-free survival than placebo (5-year rate of recurrence-free survival, 55.4% [95% confidence interval (CI), 50.8 to 59.8] vs. 38.3% [95% CI, 33.9 to 42.7]; hazard ratio for recurrence or death, 0.61 [95% CI, 0.51 to 0.72]) and a longer distant metastasis-free survival (5-year rate of distant metastasis-free survival, 60.6% [95% CI, 56.0 to 64.9] vs. 44.5% [95% CI, 39.9 to 48.9]; hazard ratio for distant metastasis or death, 0.62 [95% CI, 0.52 to 0.75]). Similar findings were obtained in the subgroup of 853 patients with PD-L1–positive tumors.ConclusionsThe 5-year analysis of adjuvant therapy with pembrolizumab resulted in a sustained improvement in the long-term recurrence- and distant metastasis-free survival compared with placebo in patients with resected stage III melanoma. (Funded by Merck & Co., Inc.; ClinicalTrials.gov number, NCT02362594, and EudraCT number, 2014-004944-37.)