Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
- PMID: 29658430
- DOI: 10.1056/NEJMoa1802357
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
Abstract
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 .).
Comment in
-
Adjuvant Therapy for Melanoma Prolongs RFS.Cancer Discov. 2018 Jun;8(6):666-667. doi: 10.1158/2159-8290.CD-NB2018-047. Epub 2018 Apr 15. Cancer Discov. 2018. PMID: 29657137
-
The new era of adjuvant therapies for melanoma.Nat Rev Clin Oncol. 2018 Sep;15(9):535-536. doi: 10.1038/s41571-018-0048-5. Nat Rev Clin Oncol. 2018. PMID: 29849093 No abstract available.
-
Immune Checkpoint Blockade across the Cancer Care Continuum.Immunity. 2018 Jun 19;48(6):1077-1080. doi: 10.1016/j.immuni.2018.06.003. Immunity. 2018. PMID: 29924973
-
Adjuvant Pembrolizumab in Resected Stage III Melanoma.N Engl J Med. 2018 Aug 9;379(6):593. doi: 10.1056/NEJMc1807505. N Engl J Med. 2018. PMID: 30091350 No abstract available.
Similar articles
-
Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial.Lancet Oncol. 2021 May;22(5):643-654. doi: 10.1016/S1470-2045(21)00065-6. Epub 2021 Apr 12. Lancet Oncol. 2021. PMID: 33857412 Clinical Trial.
-
Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.Lancet Oncol. 2021 May;22(5):655-664. doi: 10.1016/S1470-2045(21)00081-4. Epub 2021 Apr 12. Lancet Oncol. 2021. PMID: 33857414 Clinical Trial.
-
Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial.J Clin Oncol. 2020 Nov 20;38(33):3925-3936. doi: 10.1200/JCO.20.02110. Epub 2020 Sep 18. J Clin Oncol. 2020. PMID: 32946353 Free PMC article. Clinical Trial.
-
Safety of pembrolizumab for resected stage III melanoma.Expert Opin Drug Saf. 2020 Oct;19(10):1221-1227. doi: 10.1080/14740338.2020.1811228. Epub 2020 Aug 24. Expert Opin Drug Saf. 2020. PMID: 32799585 Review.
-
Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis.Oncologist. 2017 Apr;22(4):470-479. doi: 10.1634/theoncologist.2016-0419. Epub 2017 Mar 8. Oncologist. 2017. PMID: 28275115 Free PMC article. Review.
Cited by
-
Management of Localized Melanoma in the Anti-PD-1 Era.Curr Oncol Rep. 2024 Jun 6. doi: 10.1007/s11912-024-01556-z. Online ahead of print. Curr Oncol Rep. 2024. PMID: 38842606 Review.
-
Beyond Immune Checkpoint Inhibitors: Emerging Targets in Melanoma Therapy.Curr Oncol Rep. 2024 Jul;26(7):826-839. doi: 10.1007/s11912-024-01551-4. Epub 2024 May 25. Curr Oncol Rep. 2024. PMID: 38789670 Review.
-
Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology (Basel). 2024 Apr 28;13(5):307. doi: 10.3390/biology13050307. Biology (Basel). 2024. PMID: 38785789 Free PMC article. Review.
-
For the Long Haul: Management of Long-Term Survivors after Melanoma Systemic Therapy.Curr Oncol Rep. 2024 Jul;26(7):804-817. doi: 10.1007/s11912-024-01541-6. Epub 2024 May 23. Curr Oncol Rep. 2024. PMID: 38780676 Review.
-
The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.Front Oncol. 2024 May 2;14:1381250. doi: 10.3389/fonc.2024.1381250. eCollection 2024. Front Oncol. 2024. PMID: 38756658 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials