Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma.
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ICR Author
Author
Eggermont, AMM
Blank, CU
Mandala, M
Long, GV
Atkinson, V
Dalle, S
Haydon, A
Lichinitser, M
Khattak, A
Carlino, MS
Sandhu, S
Larkin, J
Puig, S
Ascierto, PA
Rutkowski, P
Schadendorf, D
Koornstra, R
Hernandez-Aya, L
Maio, M
van den Eertwegh, AJM
Grob, J-J
Gutzmer, R
Jamal, R
Lorigan, P
Ibrahim, N
Marreaud, S
van Akkooi, ACJ
Suciu, S
Robert, C
Type
Journal Article
Metadata
Show full item recordAbstract
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 .).
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Subject
Humans
Melanoma
Skin Neoplasms
Neoplasm Recurrence, Local
Adjuvants, Immunologic
Neoplasm Staging
Disease-Free Survival
Infusions, Intravenous
Survival Rate
Double-Blind Method
Quality of Life
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Intention to Treat Analysis
Kaplan-Meier Estimate
Antibodies, Monoclonal, Humanized
B7-H1 Antigen
Research team
Melanoma and Kidney Cancer
Melanoma and Kidney Cancer
Language
eng
Date accepted
2018-04-15
Citation
The New England journal of medicine, 2018, 378 (19), pp. 1789 - 1801