{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:17:50Z","timestamp":1788380270021,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Studies indicated that afatinib combined with angiogenesis inhibitor may achieve promising efficacy in non\u2010small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (<jats:italic>EGFR<\/jats:italic>) mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a multicenter, Phase II trial to explore the efficacy and safety of afatinib plus bevacizumab at first\u2010line setting for <jats:italic>EGFR<\/jats:italic>\u2010mutant NSCLC patients. The primary end point was progression\u2010free survival (PFS). The secondary end point included objective response rate (ORR), disease control rate (DCR) and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between July 11, 2020 and November 11, 2021, 54 treatment\u2010na\u00efve NSCLC patients were enrolled in the afatinib plus bevacizumab combination cohort. Meanwhile, 81 NSCLC patients with <jats:italic>EGFR<\/jats:italic> mutations treated with first\u2010line afatinib monotherapy were retrospectively collected. The median follow\u2010up time was 26.6\u2009months. No significant difference in PFS was observed between the afatinib plus bevacizumab combination cohort and the afatinib monotherapy cohort (14.5 vs. 12.2\u2009months, HR 0.87, <jats:italic>p<\/jats:italic>\u2009=\u20090.15), confirmed by propensity score matching (PSM) analysis. Patients with pleural metastasis (HR 0.56, 95% CI: 0.32\u20130.98, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and uncommon <jats:italic>EGFR<\/jats:italic> mutations (HR 0.61, 95% CI: 0.25\u20131.47, <jats:italic>p<\/jats:italic>\u2009=\u20090.05) experienced longer PFS in the combination cohort. ORR in the combination cohort is more favorable than in the afatinib monotherapy cohort (77.8% vs. 42.0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Diarrhea was the most common treatment\u2010related adverse events (TRAEs). 11.1% (6\/54) patients had grade \u2265\u20093 TRAEs when treated with afatinib plus bevacizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Afatinib combined with bevacizumab is well tolerated with moderate efficacy among patients with NSCLC, which might be a prospective strategy for patients with uncommon <jats:italic>EGFR<\/jats:italic> mutations and pleural metastasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>\n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chictr.org.cn\/\">www.chictr.org.cn<\/jats:ext-link>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.70137","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:29:36Z","timestamp":1754908176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Afatinib Plus Bevacizumab as First\u2010Line Treatment for Advanced <scp>NSCLC<\/scp> Patients With Epidermal Growth Factor Receptor (<i>EGFR<\/i>) Mutations: A Multicenter, Phase <scp>II<\/scp> Trial"],"prefix":"10.1111","volume":"16","author":[{"given":"Huiyang","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaohan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-325X","authenticated-orcid":false,"given":"Junling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4462-2931","authenticated-orcid":false,"given":"Shi","family":"Jin","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital &amp; Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2489-7791","authenticated-orcid":false,"given":"Minglei","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital\/Beijing Institute of Cancer Prevention and Treatment, Key Laboratory of Malignant Tumor Pathogenesis and Transformation Research of Ministry of Education, First Department of Thoracic Cancer, Peking University Cancer Hospital\/Beijing Cancer Prevention and Treatment Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Oncology Changzhi People's Hospital Affiliated to Changzhi Medical College  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology Luhe Hospital Affiliated to Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yang","sequence":"additional","affiliation":[{"name":"National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing P. 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