{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T01:24:52Z","timestamp":1780363492975,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non\u2010small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR\u2010TKIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Patients who developed resistance after using first\u2010 or second\u2010generation EGFR\u2010TKIs as their first\u2010line regimen without <jats:italic>EGFR<\/jats:italic> T790M mutation or had disease progression after being treated with third\u2010generation EGFR\u2010TKIs as first\u2010 or second\u2010line therapy were enrolled. All patients received toripalimab (240\u2009mg\/day on Day 1, intravenously) combined with anlotinib (12\u2009mg\/day, Days 1\u201314, orally) once every 3\u2009weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression\u2010free survival (PFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1\u2009months (95% CI 0.251\u20133.949). Grade \u22653 treatment\u2010related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12\/19), fatigue (9\/19), and hypertension (8\/19). Patients in stable disease (SD) group had lower abundance of <jats:italic>EGFR<\/jats:italic> mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (<jats:italic>p<\/jats:italic>\u2009=\u20090.031). Patients without detectable <jats:italic>EGFR<\/jats:italic> mutation (EGFR\u2212) had longer PFS compared to the ones with <jats:italic>EGFR<\/jats:italic> mutations (<jats:italic>p<\/jats:italic>\u2009=\u20090.059). Patients with high levels of soluble programmed cell death ligand 1 (PD\u2010L1) at baseline also tended to have longer PFS (<jats:italic>p<\/jats:italic>\u2009=\u20090.160).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Toripalimab combined with anlotinib was tolerable in EGFR\u2010TKI\u2010resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable <jats:italic>EGFR<\/jats:italic> mutation and high soluble PD\u2010L1 levels may benefit from this chemotherapy\u2010free treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6545","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T05:15:35Z","timestamp":1695100535000},"page":"19438-19448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The efficacy and safety of chemo\u2010free therapy in epidermal growth factor receptor tyrosine kinase inhibitor\u2010resistant advanced non\u2010small cell lung cancer: A single\u2010arm, phase II study"],"prefix":"10.1002","volume":"12","author":[{"given":"Shuyang","family":"Zhang","sequence":"first","affiliation":[{"name":"Cancer Center, Beijing Tongren Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-9586","authenticated-orcid":false,"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Radiation Sickness Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Yang","sequence":"additional","affiliation":[{"name":"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":"Guangjian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Comprehensive 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":"Xueliang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Shanghai Junshi Biosciences Co., Ltd.  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