Shitara, Kohei, Ajani, Jaffer A., Moehler, Markus, Garrido, Marcelo, Gallardo, Carlos, Shen, Lin, Yamaguchi, Kensei, Wyrwicz, Lucjan, Skoczylas, Tomasz ORCID: 0000-0002-1276-3828, Bragagnoli, Arinilda Campos, Liu, Tianshu, Tehfe, Mustapha, Elimova, Elena, Bruges, Ricardo, Zander, Thomas, de Azevedo, Sergio, Kowalyszyn, Ruben, Pazo-Cid, Roberto, Schenker, Michael ORCID: 0000-0003-2645-6391, Cleary, James M., Yanez, Patricio, Feeney, Kynan, Karamouzis, Michalis, V, Poulart, Valerie, Lei, Ming, Xiao, Hong, Kondo, Kaoru, Li, Mingshun and Janjigian, Yelena Y. (2022). Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature, 603 (7903). S. 942 - 963. BERLIN: NATURE PORTFOLIO. ISSN 1476-4687

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Abstract

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma(1-4). Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial(5) (programmed death ligand-1 (PD-L1) combined positive score >= 5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries(6). Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively(7-)(11). Treatment combining 1 mg kg(-1) nivolumab with 3 mg kg(-1) ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer(12). Here we report both long-term follow-up results comparing nivolumab plus chemotherapyversus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive >= 5 score (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score >= 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shitara, KoheiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ajani, Jaffer A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moehler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garrido, MarceloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallardo, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shen, LinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamaguchi, KenseiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wyrwicz, LucjanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skoczylas, TomaszUNSPECIFIEDorcid.org/0000-0002-1276-3828UNSPECIFIED
Bragagnoli, Arinilda CamposUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, TianshuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tehfe, MustaphaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elimova, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruges, RicardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Azevedo, SergioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kowalyszyn, RubenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pazo-Cid, RobertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenker, MichaelUNSPECIFIEDorcid.org/0000-0003-2645-6391UNSPECIFIED
Cleary, James M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yanez, PatricioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feeney, KynanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karamouzis, Michalis, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poulart, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lei, MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xiao, HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kondo, KaoruUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, MingshunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janjigian, Yelena Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-696920
DOI: 10.1038/s41586-022-04508-4
Journal or Publication Title: Nature
Volume: 603
Number: 7903
Page Range: S. 942 - 963
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OPEN-LABEL; COMBINATION THERAPY; SOLID TUMORS; JUNCTION; CAPECITABINE; CISPLATINMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69692

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