{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:34:53Z","timestamp":1740123293637,"version":"3.37.3"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg\/m<jats:sup>2<\/jats:sup>) and etoposide (100 mg\/m<jats:sup>2<\/jats:sup>; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg\/mL\/min) and etoposide (100 mg\/m<jats:sup>2<\/jats:sup>; days 1, 2, 3) in cohort 2; or with cisplatin\/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3. Combination therapy was followed by pembrolizumab monotherapy (31 cycles). The primary endpoint was safety and tolerability (including dose-limiting toxicities; DLTs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Fifteen patients were included in the study (cohort 1, n = 6; cohort 2, n = 6; cohort 3, n = 3). Median time from treatment allocation to data cutoff was 22.1 months (range, 4.1\u201232.4 months). DLTs occurred in 3 patients in cohort 1 (one patient with grade 4 laryngeal stenosis and grade 3 febrile neutropenia; two patients with grade 3 febrile neutropenia); no patients in cohorts 2 or 3 experienced DLTs. Grade \u2265 3 treatment-related adverse events included leukopenia (67%) and neutropenia (87%). Among all patients, ORR was 67% (95% CI, 38%\u201288%) and median DOR was 4.5 months (range, 2.8\u201228.8 months). Median PFS was 4.2 months (95% CI, 3.0\u20127.8 months) and median OS was 22.1 months (95% CI, 7.4\u201225.9 months).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Pembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial Registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/\">ClinicalTrials.gov<\/jats:ext-link>, NCT01840579.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10637-023-01411-1","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T11:02:08Z","timestamp":1706785328000},"page":"136-144","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-4681","authenticated-orcid":false,"given":"Naoyuki","family":"Nogami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Tokito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Zenke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyako","family":"Satouchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Seto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Saka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Ohtani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirong","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,1]]},"reference":[{"key":"1411_CR1","unstructured":"Foundation for Promotion of Cancer Research (2021) Cancer statistics in Japan - 2021. https:\/\/ganjoho.jp\/public\/qa_links\/report\/statistics\/pdf\/cancer_statistics_2021.pdf. 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The trial was conducted in accordance with Good Clinical Practice guidelines and in compliance with the Declaration of Helsinki. Patients provided informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Dr. Nogami reports receiving lecture fees, honoraria, or other fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., and Eli Lilly Japan. Takaaki Tokito has received honoraria for lectures from Chugai Pharmaceutical, AstraZeneca, MSD, and Novartis. Yoshitaka Zenke has received payment or honoraria from AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Takeda Pharmaceutical, Boehringer-Ingelheim, Taiho, MSD, Novartis, Pfizer, Nippon-Kayaku, and Kyowa-Hakko Kirin; institution has received grants or contracts from MSD, Merck, AstraZeneca, Daiichi-Sankyo, and Amgen. Miyako Satouchi has received honoraria (lecture fees) from Chugai, AstraZeneca, Eli Lilly, Taiho, MSD, Pfizer, Novartis, Bristol-Myers Squibb, Ono, Takeda, Daiichi-Sankyo, Amgen, and Merck; and has received clinical trial funding from Chugai, AstraZeneca, MSD, Janssen, Amgen, Taiho, Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, and Eisai. Takashi Seto has received honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, and Towa Pharmaceutical; institution has received grants or contracts from AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, and Pfizer Japan. Hideo Saka has received honoraria from Boston Scientific, Taiho, AstraZeneca, Ono, Boehringer-Ingelheim, Fuji film, JSRE, Eli Lilly, Chugai, Kaneka, and Century-Medical; has received research funding from Boston Scientific, MSD, AstraZeneca, Ono, Parexel International, WJOG, Celgene, and Taisho-Toyama. Junko Ohtani, Shirong Han, and Kazuo Noguchi are employees of MSD K.K., Tokyo, Japan. Makoto Nishio has received grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceuticals, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Company Limited; and has received personal fees from Boehringer-Ingelheim, Merck Biopharma, Teijin Pharma Limited, and AbbVie.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}