Adjuvant pembrolizumab versus placebo in resected stage III melanoma.
Authors
Eggermont, ABlank, C
Mandala, M
Long, G
Atkinson, V
Dalle, S
Haydon, A
Lichinitser, M
Khattak, A
Carlino, M
Sandhu, S
Larkin, J
Puig, S
Ascierto, P
Rutkowski, P
Schadendorf, D
Koornstra, R
Hernandez-Aya, L
Maio, M
van den Eertwegh, A
Grob, J
Gutzmer, R
Jamal, R
Lorigan, Paul C
Ibrahim, N
Marreaud, S
van Akkooi, ACJ
Suciu, S
Robert, C
Affiliation
Gustave Roussy Cancer Campus Grand Paris and University Paris-Saclay, VillejuifIssue Date
2018-04-15
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Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. Results At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group. Conclusions 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. (Funded by Merck; ClinicalTrials.gov number, NCT02362594 ; EudraCT number, 2014-004944-37 .).Citation
Adjuvant pembrolizumab versus placebo in resected stage III melanoma. 2018 N Engl J MedJournal
The New England Journal of MedicineDOI
10.1056/NEJMoa1802357PubMed ID
29658430Type
ArticleLanguage
enISSN
1533-4406ae974a485f413a2113503eed53cd6c53
10.1056/NEJMoa1802357
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