dc.contributor.author | Doki, Y | |
dc.contributor.author | Ajani, JA | |
dc.contributor.author | Kato, K | |
dc.contributor.author | Xu, J | |
dc.contributor.author | Wyrwicz, L | |
dc.contributor.author | Motoyama, S | |
dc.contributor.author | Ogata, T | |
dc.contributor.author | Kawakami, H | |
dc.contributor.author | Hsu, C-H | |
dc.contributor.author | Adenis, A | |
dc.contributor.author | El Hajbi, F | |
dc.contributor.author | Di Bartolomeo, M | |
dc.contributor.author | Braghiroli, MI | |
dc.contributor.author | Holtved, E | |
dc.contributor.author | Ostoich, SA | |
dc.contributor.author | Kim, HR | |
dc.contributor.author | Ueno, M | |
dc.contributor.author | Mansoor, W | |
dc.contributor.author | Yang, W-C | |
dc.contributor.author | Liu, T | |
dc.contributor.author | Bridgewater, J | |
dc.contributor.author | Makino, T | |
dc.contributor.author | Xynos, I | |
dc.contributor.author | Liu, X | |
dc.contributor.author | Lei, M | |
dc.contributor.author | Kondo, K | |
dc.contributor.author | Patel, A | |
dc.contributor.author | Gricar, J | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Kitagawa, Y | |
dc.contributor.author | CheckMate 648 Trial Investigators | |
dc.date.accessioned | 2022-04-27T12:28:40Z | |
dc.date.available | 2022-04-27T12:28:40Z | |
dc.identifier.citation | The New England journal of medicine, 2022, 386 (5), pp. 449 - 462 | en |
dc.identifier.issn | 0028-4793 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5102 | |
dc.identifier.eissn | 1533-4406 | en_US |
dc.identifier.eissn | 1533-4406 | |
dc.identifier.doi | 10.1056/nejmoa2111380 | en_US |
dc.identifier.doi | 10.1056/nejmoa2111380 | |
dc.description.abstract | <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.). | en |
dc.format | Print | en_US |
dc.format.extent | 449 - 462 | en_US |
dc.language | eng | en_US |
dc.language.iso | eng | en |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en |
dc.subject | CheckMate 648 Trial Investigators | en |
dc.subject | Humans | en |
dc.subject | Carcinoma, Squamous Cell | en |
dc.subject | Esophageal Neoplasms | en |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | en |
dc.subject | Survival Analysis | en |
dc.subject | Adult | en |
dc.subject | Aged | en |
dc.subject | Aged, 80 and over | en |
dc.subject | Middle Aged | en |
dc.subject | Female | en |
dc.subject | Male | en |
dc.subject | Ipilimumab | en |
dc.subject | B7-H1 Antigen | en |
dc.subject | Nivolumab | en |
dc.subject | Progression-Free Survival | en |
dc.subject | Immune Checkpoint Inhibitors | en |
dc.title | Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. | en |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-02-03 | |
rioxxterms.version | VoR | en |
rioxxterms.versionofrecord | 10.1056/nejmoa2111380 | en |
dc.relation.isPartOf | The New England journal of medicine | en_US |
pubs.issue | 5 | en_US |
pubs.notes | Not known | en_US |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | en_US |
pubs.volume | 386 | en_US |
pubs.embargo.terms | Not known | en_US |
dc.contributor.icrauthor | Chau, Ian | |