{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:00:57Z","timestamp":1760576457543,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":9,"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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Second\u2010generation anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and brigatinib, are widely used in patients with ALK\u2010positive non\u2010small cell lung cancer (NSCLC) who develop resistance or progress on crizotinib. However, real\u2010world data comparing their efficacy and safety remain limited. This multicenter, prospective cohort study compared the clinical outcomes of alectinib and brigatinib in this setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with stage IV ALK\u2010positive NSCLC who progressed on crizotinib were enrolled and treated with either brigatinib or alectinib. The primary endpoint was the progression\u2010free survival (PFS) rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty patients were included (brigatinib, <jats:italic>n<\/jats:italic>\u2009=\u200934; alectinib, <jats:italic>n<\/jats:italic>\u2009=\u200926). Median follow\u2010up durations were 26.5 and 30.0\u2009months. Disease progression or death occurred in 50.0% (brigatinib) and 46.2% (alectinib), respectively. The 3\u2010year PFS was 51.5% (brigatinib) vs. 62.1% (alectinib), with no significant difference at 5\u2009years (40.0% vs. 42.5%; <jats:italic>p<\/jats:italic>\u2009=\u20090.260). Overall response rates were similar (58.8% vs. 46.2%; <jats:italic>p<\/jats:italic>\u2009=\u20090.475). However, intracranial outcomes appeared more favorable with alectinib: the 3\u2010year intracranial PFS was 70.5% vs. 31.7% (<jats:italic>p<\/jats:italic>\u2009=\u20090.023), and intracranial ORR was 94.4% vs. 64.3% (<jats:italic>p<\/jats:italic>\u2009=\u20090.028). More patients in the brigatinib group had prior whole\u2010brain radiotherapy (21.4% vs. 5.6%), while radiosurgery was more frequent in the alectinib group (55.6% vs. 35.7%). Treatment discontinuation rates due to adverse events were comparable between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In crizotinib\u2010refractory ALK\u2010positive NSCLC, systemic efficacy was not significantly different between brigatinib and alectinib; however, alectinib was associated with more favorable intracranial PFS and ORR, which may be partly explained by differences in prior brain\u2010directed local treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.70175","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:10:17Z","timestamp":1760159417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World Outcomes of Brigatinib Compared to Alectinib as a Second\u2010Line Therapy After Crizotinib in Advanced Anaplastic Lymphoma Kinase Positive Non\u2010Small Cell Lung Cancer Patients"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0073-2079","authenticated-orcid":false,"given":"Min Jee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Seok","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Nim","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol\u2010Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chonnam National University Medical School  Hwasun Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chonnam National University Medical School  Hwasun Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u2010Jae","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chonnam National University Medical School  Hwasun Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-737X","authenticated-orcid":false,"given":"Jun Hyeok","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong\u2010Seon","family":"Ryu","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Min","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of 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