{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:07:54Z","timestamp":1790356074922,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["Bristol-Myers Squibb"],"award-info":[{"award-number":["Bristol-Myers Squibb"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","award":["Ono Pharmaceutical"],"award-info":[{"award-number":["Ono Pharmaceutical"]}],"id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nivolumab plus ipilimumab-based therapies have shown long-term, durable clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC), including those with tumor programmed death-ligand 1 (PD-L1) expression &lt; 1%, a population with high unmet need. Here we report long-term clinical outcomes with first-line nivolumab plus ipilimumab with or without chemotherapy (2 cycles) versus chemotherapy (\u2264 4 cycles) in a pooled population of Japanese patients with metastatic NSCLC and tumor PD-L1 &lt; 1% from the randomized, phase 3 CheckMate 227 (NCT02477826) and CheckMate 9LA (NCT03215706) studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adults with stage IV\/recurrent NSCLC without sensitizing\n                      <jats:italic>EGFR<\/jats:italic>\n                      \/\n                      <jats:italic>ALK<\/jats:italic>\n                      alterations were included. Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the pooled population of Japanese patients with tumor PD-L1\u00a0&lt;\u00a01% in the nivolumab plus ipilimumab with or without chemotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      = 34) versus chemotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      = 41) arms, median OS was 41.0 (95% CI 19.4\u2013not reached) versus 15.2 (95% CI 7.6\u201321.3) months (hazard ratio [HR] 0.46; 95% CI 0.27\u20130.78); 5-year OS rates were 38% (95% CI 22\u201354) versus 16% (95% CI 6\u201330). Median PFS was 8.2 (95% CI 4.1\u201319.3) versus 5.6 (95% CI 4.2\u20137.0) months (HR 0.57 [95% CI 0.31\u20131.03]). No new safety signals were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Consistent with results in the pooled global population, nivolumab plus ipilimumab with or without chemotherapy showed long-term, durable clinical benefit in Japanese patients with metastatic NSCLC and tumor PD-L1 &lt; 1%, suggesting potential clinical benefit with its use as a first-line treatment for this hard-to-treat population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-026-03116-w","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:46:41Z","timestamp":1786448801000},"page":"2179-2190","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nivolumab plus ipilimumab-based treatment in Japanese patients with metastatic non-small cell lung cancer and tumor PD-L1 &lt; 1%: a pooled analysis"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-4165","authenticated-orcid":false,"given":"Makoto","family":"Nishio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Tambo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Hotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruko","family":"Daga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Masubuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takekazu","family":"Aoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Tschaika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Mizutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"11","key":"3116_CR1","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1016\/j.jtho.2023.09.076","volume":"18","author":"SS Ramalingam","year":"2023","unstructured":"Ramalingam SS, Ciuleanu TE, Bernabe Caro R et al (2023) OA14.03 six-year survival and HRQoL outcomes with 1L nivolumab + ipilimumab in patients with metastatic NSCLC from CheckMate227. 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Hidetoshi Hayashi reports receiving honoraria from AbbVie, Amgen, AstraZeneca K.K. Bristol Myers Squibb, Chugai Pharmaceuticals, CMIC, Daiichi Sankyo, Eisai Inc., Eli Lilly Japan K.K., EPS Corporation, MSD K.K., Ono Pharmaceuticals, and Takeda Pharmaceuticals; research funding from A2 Healthcare Corp, AbbVie, Amgen, Astellas Pharma, AstraZeneca K.K., Bristol Myers Squibb, Chugai Pharmaceuticals, Daiichi Sankyo, GlaxoSmithKline K.K., ICON Clinical Research GK, IQVIA Services JAPAN K.K., Janssen Pharmaceutical K.K., MSD K.K., Nippon Boehringer Ingelheim, Pfizer R&D Japan G.K., PPD-SNBL K.K., PRA Health Sciences Inc., Sanofi K.K., SYNEOS HEALTH CLINICAL K.K., Sysmex Corporation, Taiho Pharmaceuticals, and WJOG (West Japan Oncology Group); manuscript fees from Guardant Health Japan Corp. and Ono Pharmaceuticals; scholarship donations from Chugai Pharmaceuticals and Eisai Co. Ltd. Yasushi Goto reports receiving honoraria from AbbVie GK, Amgen K.K., AstraZeneca K.K., Asuka Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Igaku Academy YTL Co., Ltd., Janssen Pharmaceutical K.K., Johnson & Johnson, Kagaku Hyoronsha Publishing Co., Ltd., Medical Review Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sandoz K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited; research funding and manuscript fees from AstraZeneca K.K. Satoshi Ikeda reports receiving honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceuticals, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Regeneron, Taiho Pharmaceuticals, and Takeda; research funding from AstraZeneca and Chugai. Toshihide Yokoyama reports receiving honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, Eli Lilly, Janssen, MSD, Ono, Pfizer, and Takeda; research funding from AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Janssen, MSD, Parexel Internation, Pfizer, and Takeda. Hiroshi Tanaka reports receiving research funding to institution and honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, MSD, and Ono. Yuichi Tambo reports receiving honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Kirin, MSD, Pfizer, Taiho, and Takeda; research funding from AstraZeneca, Beigene, Bristol Myers Squibb, Daiichi Sankyo, Gilead, MSD, Ono, and Regeneron; grant from JSPS Kakenhi. Katsuyuki Hotta reports receiving honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Chugai, Janssen, Lilly, Merck, MSD, Nippon Kayaku, Ono, Taiho, and Takeda; research funding from AbbVie, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, MSD, and Ono. Haruko Daga reports receiving honoraria from AstraZeneca. Marina Tschaika and Takekazu Aoyama report employment and stock ownership in Bristol Myers Squibb. Nan Hu is an employee of Bristol Myers Squibb. Tatsuro Fukuhara, Ken Masubuchi, and Hideaki Mizutani have no conflicts of interest to disclose.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The institutional review board or independent ethics committee at each center approved these trials, and they were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. All patients provided written informed consent. The trial protocols have been published previously (Hellmann MD, et al.\n                      N Engl J Med\n                      2018;378:2093\u20132104; Paz-Ares, L, et al.\n                      Lancet Onc\n                      , 2021;22:198\u2013211).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}