Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma.
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ICR Author
Author
Doki, Y
Ajani, JA
Kato, K
Xu, J
Wyrwicz, L
Motoyama, S
Ogata, T
Kawakami, H
Hsu, C-H
Adenis, A
El Hajbi, F
Di Bartolomeo, M
Braghiroli, MI
Holtved, E
Ostoich, SA
Kim, HR
Ueno, M
Mansoor, W
Yang, W-C
Liu, T
Bridgewater, J
Makino, T
Xynos, I
Liu, X
Lei, M
Kondo, K
Patel, A
Gricar, J
Chau, I
Kitagawa, Y
CheckMate 648 Trial Investigators
Type
Journal Article
Metadata
Show full item recordAbstract
<h4>Background</h4>First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma.<h4>Methods</h4>In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients).<h4>Results</h4>A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P = 0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P = 0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P = 0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P = 0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone.<h4>Conclusions</h4>Both first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 648 ClinicalTrials.gov number, NCT03143153.).
Collections
Subject
CheckMate 648 Trial Investigators
Humans
Carcinoma, Squamous Cell
Esophageal Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Survival Analysis
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Ipilimumab
B7-H1 Antigen
Nivolumab
Progression-Free Survival
Immune Checkpoint Inhibitors
Language
eng
Date accepted
2022-02-03
Citation
The New England journal of medicine, 2022, 386 (5), pp. 449 - 462