{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:16:48Z","timestamp":1789075008806,"version":"build-2803163510"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Daiichi Sankyo Co. Ltd."},{"name":"T-DXd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) presents significant therapeutic challenges due to its molecular heterogeneity. Previous studies suggest that immune checkpoint inhibitors (ICIs) may enhance the efficacy of subsequent HER2-targeted therapy. However, evidence suggesting an optimal sequence for nivolumab and trastuzumab deruxtecan (T-DXd) treatment is limited. This exploratory analysis of EN-DEAVOR evaluated the effectiveness and safety of administering T-DXd relative to the timing of prior ICI administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study assessed real-world outcomes of T-DXd in patients with HER2-positive AGC stratified by prior ICI exposure: within 2\u00a0months of nivolumab (Group A), &amp;gt;2\u00a0months (Group B), and no prior nivolumab (Group C). The primary effectiveness endpoints included real-world progression-free survival (rwPFS) and objective response rate (ORR). Safety endpoints included grade\u00a0\u2265\u00a03 adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 311 eligible patients, Group A showed the longest median rwPFS (n\u00a0=\u00a063; 6.9\u00a0months) compared with Group B (n\u00a0=\u00a063; 4.6\u00a0months) and Group C (n\u00a0=\u00a0185; 4.2\u00a0months). The risk of progression was significantly lower in Group A compared with Group B (hazard ratio [95% confidence interval]: 0.6 [0.4\u20130.9]; P\u00a0=\u00a0.0074). ORR was numerically highest in Group A (54.9%) versus Group B (30.8%) and Group C (43.4%). More patients in Group B (58.7%) experienced grade\u00a0\u2265\u00a03 AEs than in Group A (50.8%) and Group C (43.8%). No new safety signals were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiating T-DXd within 2\u00a0months post-ICI may enhance therapeutic efficacy in HER2-positive AGC without affecting safety, supporting a potential sequencing option after ICI therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyaf216","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T12:39:15Z","timestamp":1766839155000},"page":"538-545","source":"Crossref","is-referenced-by-count":1,"title":["Impact of prior immune checkpoint inhibitor on trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory analysis of the EN-DEAVOR study"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-0077","authenticated-orcid":false,"given":"Yukiya","family":"Narita","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital , 1-1 Kanokoden, Chikusa Ward, Nagoya, Aichi 464-8681 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisato","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine , 2-1 Seiryomachi, Aoba Ward, Sendai, Miyagi 980-0872 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Cancer Center, Gifu University Hospital , 1-1 Yanagido, Gifu 501-1112 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotoshi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Genetic Oncology, Osaka International Cancer Institute , 3-1-69 Otemae, Chuo-ku, Osaka 540-0008 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Konishi","sequence":"additional","affiliation":[{"name":"Division of Digestive Surgery, Kyoto Prefectural University of Medicine , 465 Kajiicho, Kamigyo Ward, Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine , Yoshidakonoecho, Sakyo Ward, Kyoto 606-8303 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-7117","authenticated-orcid":false,"given":"Keiko","family":"Minashi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Chiba Cancer Center , 666-2 Nitonacho, Chuo Ward, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Imano","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kindai University Faculty of Medicine, 377-2 Onohigashi, Osakasayama, Osaka 589-0014 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rin","family":"Inamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Cancer Center , 780 Komuro, Ina, Kitaadachi District, Saitama 362-0806 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-3757","authenticated-orcid":false,"given":"Tomohiro","family":"Nishina","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, NHO Shikoku Cancer Center , 160 Minamiumemotomachi, Matsuyama, Ehime 791-0245 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Sunto-gun, Shizuoka 411-8777 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohisa","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nihonkai General Hospital , 30 Akihocho, Sakata, Yamagata 998-8501 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