{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:54:17Z","timestamp":1774947257305,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>As most patients with epidermal growth factor receptor (<jats:italic>EGFR<\/jats:italic>)\u2010mutant non\u2010small cell lung cancer (NSCLC) develop progressive disease after treatment with osimertinib, it is important to develop more effective treatment options. Afatinib has been shown to be more effective in in vitro studies than osimertinib when used in cancer cell lines containing some specific <jats:italic>EGFR<\/jats:italic> mutations. Therefore, afatinib may be an effective solution, especially when used in combination with an anti\u2010VEGF agent such as bevacizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A phase II multicenter, open\u2010label, single\u2010arm trial has been initiated to evaluate the efficacy and safety of afatinib and bevacizumab combination as salvage therapy for <jats:italic>EGFR<\/jats:italic>\u2010mutated lung cancer in patients previously treated with osimertinib. The primary endpoint will be the objective response rate (ORR) and secondary endpoints are progression\u2010free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>A previous study indicated that afatinib inhibits lung cancer cells with specific <jats:italic>EGFR<\/jats:italic> mutations more effectively than other EGFR\u2010TKIs such as osimertinib. Therefore, we expect that combination therapy using afatinib and bevacizumab will be effective in patients previously treated with osimertinib (registration no. jRCTs031190077).<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13503","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T06:21:46Z","timestamp":1591251706000},"page":"2125-2129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Afatinib + bevacizumab combination therapy in <scp><i>EGFR<\/i><\/scp>\u2010mutant <scp>NSCLC<\/scp> patients with osimertinib resistance: Protocol of an <scp>open\u2010label<\/scp>, phase <scp>II<\/scp>, multicenter, <scp>single\u2010arm<\/scp> trial"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-320X","authenticated-orcid":false,"given":"Nobuaki","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Pulmonology Yokohama City 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