{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:41:39Z","timestamp":1790721699373,"version":"4.1.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Chemoimmunotherapy is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). However, whether findings from pivotal trials can be extrapolated to the clinical practice setting remains unclear.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare treatment outcome gaps following first-line chemoimmunotherapy for patients with ES-SCLC between those who met and did not meet the eligibility criteria used in previous clinical trials.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>A prospective cohort study was conducted from September 1, 2019, to September 30, 2020, at 32 hospitals in Japan, with at least 12 months of follow-up. Participants included consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as first-line therapy.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered trial-eligible.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was 6-month progression-free survival. The secondary outcomes were differences in progression-free survival, overall survival, and safety according to whether key clinical trial eligibility criteria were met.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 207 patients were analyzed (median age, 72 years; range, 46-87 years; 170 [82%] were male). Sixty-four patients (31%) were older adults (age \u226575 years), and most (184 [89%]) had an Eastern Cooperative Oncology Group performance status of 0 or 1. There were 132 (64%) trial-eligible patients. The 6-month progression-free survival rate for all patients was 38.8% (95% CI, 32.4%-45.7%). The median progression-free survival was 5.1 months in trial-eligible patients and 4.7 months in trial-ineligible patients (hazard ratio, 0.72; 95% CI, 0.53-0.97; P<\/jats:italic>\u2009=\u2009.03). The proportion of patients who achieved disease control was 93% (118 of 127) in trial-eligible patients and 77% (55 of 71) in trial-ineligible patients (P<\/jats:italic>\u2009=\u2009.002). The median overall survival was 15.8 months in trial-eligible patients and 13.1 months in trial-ineligible patients (hazard ratio, 0.73; 95% CI, 0.51-1.07; P<\/jats:italic>\u2009=\u2009.10). The rate of severe adverse events was numerically higher among trial-ineligible patients than among trial-eligible patients (39% vs 27%; P<\/jats:italic>\u2009=\u2009.07).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, the overall treatment outcome was comparable to that reported in pivotal clinical trials. However, treatment outcomes after chemoimmunotherapy might differ between trial-eligible and trial-ineligible patients. These findings suggest that trial-eligibility criteria may be useful in clinical practice, and further studies using data from clinical practice settings are required to inform regulatory approval and clinical decision-making.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.0698","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T16:00:44Z","timestamp":1677254444000},"page":"e230698","source":"Crossref","is-referenced-by-count":27,"title":["Outcomes of Chemoimmunotherapy Among Patients With Extensive-Stage Small Cell Lung Cancer According to Potential Clinical Trial Eligibility"],"prefix":"10.1001","volume":"6","author":[{"given":"Daichi","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Internal Medicine III, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akito","family":"Hata","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Hyogo College of Medicine, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Furuya","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Sakata","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisaku","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Itami City Hospital, Itami, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Respirology, Chiba University Graduate School of Medicine, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Kanazu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Internal Medicine III, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"Internal Medicine III, Wakayama Medical University, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"issue":"1","key":"zoi230044r1","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/s41598-017-01571-0","article-title":"Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages.","volume":"7","author":"Wang","year":"2017","journal-title":"Sci Rep"},{"issue":"5","key":"zoi230044r2","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1002\/cncr.29098","article-title":"Small cell lung cancer: where do we go from here?","volume":"121","author":"Byers","year":"2015","journal-title":"Cancer"},{"issue":"23","key":"zoi230044r3","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer.","volume":"379","author":"Horn","year":"2018","journal-title":"N Engl J Med"},{"issue":"10212","key":"zoi230044r4","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial.","volume":"394","author":"Paz-Ares","year":"2019","journal-title":"Lancet"},{"issue":"1","key":"zoi230044r5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S1470-2045(20)30539-8","article-title":"Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial.","volume":"22","author":"Goldman","year":"2021","journal-title":"Lancet Oncol"},{"issue":"6","key":"zoi230044r6","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1200\/JCO.20.01055","article-title":"Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133).","volume":"39","author":"Liu","year":"2021","journal-title":"J Clin Oncol"},{"issue":"1","key":"zoi230044r7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/JTO.0b013e3181fb50d8","article-title":"Barriers to enrollment in non\u2013small cell lung cancer therapeutic clinical trials.","volume":"6","author":"Baggstrom","year":"2011","journal-title":"J Thorac Oncol"},{"issue":"5","key":"zoi230044r8","doi-asserted-by":"publisher","first-page":"e721","DOI":"10.1016\/j.cllc.2018.05.014","article-title":"Clinical characteristics and prognosis of patients with advanced non\u2013small-cell lung cancer who are ineligible for clinical trials.","volume":"19","author":"Kawachi","year":"2018","journal-title":"Clin Lung Cancer"},{"issue":"1","key":"zoi230044r9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.cllc.2012.03.008","article-title":"Identifying barriers associated with enrollment of patients with lung cancer into clinical trials.","volume":"14","author":"Horn","year":"2013","journal-title":"Clin Lung Cancer"},{"issue":"23","key":"zoi230044r10","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1056\/NEJMsb1609216","article-title":"Real-world evidence\u2014what is it and what can it tell us?","volume":"375","author":"Sherman","year":"2016","journal-title":"N Engl J Med"},{"issue":"5","key":"zoi230044r11","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41571-019-0167-7","article-title":"Real-world data: towards achieving the achievable in cancer care.","volume":"16","author":"Booth","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"zoi230044r12","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.ccell.2021.05.012","article-title":"Using real-word data to evaluate the effects of broadening eligibility criteria in oncology trials.","volume":"39","author":"Sanz-Garcia","year":"2021","journal-title":"Cancer Cell"},{"key":"zoi230044r13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102031","article-title":"Real world data in the era of immune checkpoint inhibitors (ICIs): increasing evidence and future applications in lung cancer.","volume":"87","author":"Pasello","year":"2020","journal-title":"Cancer Treat Rev"},{"issue":"7","key":"zoi230044r14","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.annonc.2021.03.199","article-title":"Immunotherapy use outside clinical trial populations: never say never?","volume":"32","author":"Rzeniewicz","year":"2021","journal-title":"Ann Oncol"},{"issue":"12","key":"zoi230044r15","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1001\/jamaoncol.2021.4971","article-title":"Uptake and survival outcomes following immune checkpoint inhibitor therapy among trial-ineligible patients with advanced solid cancers.","volume":"7","author":"Parikh","year":"2021","journal-title":"JAMA Oncol"},{"issue":"10294","key":"zoi230044r16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"issue":"10302","key":"zoi230044r17","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/S0140-6736(21)01234-4","article-title":"Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study.","volume":"398","author":"Sun","year":"2021","journal-title":"Lancet"},{"issue":"22","key":"zoi230044r18","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1056\/NEJMoa1809615","article-title":"Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer.","volume":"379","author":"Schmid","year":"2018","journal-title":"N Engl J Med"},{"issue":"10212","key":"zoi230044r19","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/S0140-6736(19)32591-7","article-title":"Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study.","volume":"394","author":"Burtness","year":"2019","journal-title":"Lancet"},{"issue":"20","key":"zoi230044r20","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"issue":"3","key":"zoi230044r21","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0169-5002(02)00072-7","article-title":"Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer\u2014what limits limited disease?","volume":"37","author":"Micke","year":"2002","journal-title":"Lung Cancer"},{"issue":"15","key":"zoi230044r22","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1200\/JCO.19.02035","article-title":"Informing patients about expected outcomes: the efficacy-effectiveness gap.","volume":"38","author":"Templeton","year":"2020","journal-title":"J Clin Oncol"},{"issue":"8","key":"zoi230044r23","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1002\/cncr.32697","article-title":"Assessing the efficacy-effectiveness gap for cancer therapies: a comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.","volume":"126","author":"Phillips","year":"2020","journal-title":"Cancer"},{"key":"zoi230044r24","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.ejca.2021.07.001","article-title":"Real-world outcomes associated with new cancer medicines approved by the Food and Drug Administration and European Medicines Agency: a retrospective cohort study.","volume":"155","author":"Boyle","year":"2021","journal-title":"Eur J Cancer"},{"issue":"12","key":"zoi230044r25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2021.100249","article-title":"A real-world evaluation of atezolizumab plus platinum-etoposide chemotherapy in patients with extensive-stage SCLC in Canada.","volume":"2","author":"Elegbede","year":"2021","journal-title":"JTO Clin Res Rep"},{"issue":"2","key":"zoi230044r26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2021.100265","article-title":"A real-world study on the effectiveness and safety of pembrolizumab plus chemotherapy for nonsquamous NSCLC.","volume":"3","author":"Fujimoto","year":"2021","journal-title":"JTO Clin Res Rep"},{"key":"zoi230044r27","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.lungcan.2019.11.014","article-title":"Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: a multicenter retrospective observational study in Japan.","volume":"140","author":"Morita","year":"2020","journal-title":"Lung Cancer"},{"issue":"1","key":"zoi230044r29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/cpt.2019.106.issue-1","article-title":"The US Food and Drug Administration\u2019s real-world evidence framework: a commitment for engagement and transparency on real-world evidence.","volume":"106","author":"ElZarrad","year":"2019","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"zoi230044r30","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/s41571-020-0345-7","article-title":"Real-world evidence and regulatory drug approval.","volume":"17","author":"Raphael","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"zoi230044r31","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.annonc.2021.12.015","article-title":"External control arms in oncology: current use and future directions.","volume":"33","author":"Mishra-Kalyani","year":"2022","journal-title":"Ann Oncol"},{"issue":"10","key":"zoi230044r32","doi-asserted-by":"publisher","first-page":"e456","DOI":"10.1016\/S1470-2045(21)00488-5","article-title":"Leveraging external data in the design and analysis of clinical trials in neuro-oncology.","volume":"22","author":"Rahman","year":"2021","journal-title":"Lancet Oncol"},{"issue":"16","key":"zoi230044r33","doi-asserted-by":"publisher","first-page":"4993","DOI":"10.1158\/1078-0432.CCR-19-0820","article-title":"Design and evaluation of an external control arm using prior clinical trials and real-world data.","volume":"25","author":"Ventz","year":"2019","journal-title":"Clin Cancer Res"},{"issue":"5","key":"zoi230044r34","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41568-019-0133-9","article-title":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.","volume":"19","author":"Rudin","year":"2019","journal-title":"Nat Rev Cancer"},{"issue":"12","key":"zoi230044r35","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1016\/j.jtho.2020.09.009","article-title":"SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization.","volume":"15","author":"Baine","year":"2020","journal-title":"J Thorac Oncol"},{"key":"zoi230044r28","unstructured":"US Food and Drug Administration. Real-world evidence. December 12, 2022. Accessed April 1, 2022. https:\/\/www.fda.gov\/science-research\/science-and-research-special-topics\/real-world-evidence"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2801814\/fujimoto_2023_oi_230044_1676647645.08625.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T16:00:48Z","timestamp":1677254448000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2801814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.0698","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}