{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:49:59Z","timestamp":1787161799994,"version":"build-2736575974"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"\n Importance<\/jats:title>\n The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (\n EGFR<\/jats:italic>\n )\u2013sensitizing variants assessed by circulating tumor DNA (ctDNA).\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n The Efficiency of Icotinib in Plasma ctDNA\n EGFR<\/jats:italic>\n Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma\n EGFR<\/jats:italic>\n -sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA\n EGFR<\/jats:italic>\n variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with\n EGFR<\/jats:italic>\n variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based\n EGFR<\/jats:italic>\n genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03346811<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.2719","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T11:00:53Z","timestamp":1658401253000},"page":"1328","source":"Crossref","is-referenced-by-count":17,"title":["Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With\n EGFR<\/i>\n -Sensitizing Variants Assessed by Circulating Tumor DNA Testing"],"prefix":"10.1001","volume":"8","author":[{"given":"Jiachen","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Handan Central Hospital, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tangshan People\u2019s Hospital, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiming","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Liaoning Cancer Hospital, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Affiliated Hospital of Chengde Medical University, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Xingtai People\u2019s Hospital, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diansheng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, North China University of Science and Technology Affiliated Hospital, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Affiliated Hospital of Hangzhou Normal University (Hangzhou Second People\u2019s Hospital), Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cangzhou Central Hospital, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Qinhuangdao Cancer Hospital\/The Fourth Hospital of Qinhuangdao, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, First Hospital of Qinhuangdao, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beijing Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Shaoxing People\u2019s Hospital, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolan","family":"Li","sequence":"additional","affiliation":[{"name":"Comprehensive Family\/Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Comprehensive Family\/Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, 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Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Hangzhou Repugene Technology, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchun","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 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