{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T13:25:03Z","timestamp":1787405103022,"version":"build-2736575974"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2022KY629"],"award-info":[{"award-number":["2022KY629"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The phase III CROWN study established lorlatinib as a standard first-line therapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). In routine practice, it may be used upfront or after a second-generation (2G) ALK tyrosine kinase inhibitor (TKI), but real-world lorlatinib-specific systemic and central nervous system (CNS) outcomes by timing remain inadequately defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare lorlatinib-specific progression-free survival (PFS), tumor response, overall survival (OS), CNS-first progression, and safety between 1L lorlatinib and Post-2G lorlatinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Single-center, retrospective, real-world cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Consecutive patients with ALK-positive advanced NSCLC who initiated lorlatinib at Zhejiang Cancer Hospital between January 2023 and August 2025 were included, with follow-up updated through June 2026. Patients were classified as first-line lorlatinib (1L lorlatinib) or post-2G ALK TKI lorlatinib (Post-2G lorlatinib). The primary endpoint was lorlatinib-specific PFS from lorlatinib initiation. CNS progression was estimated using competing-risk methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 112 patients, 55 received 1L lorlatinib and 57 received Post-2G lorlatinib. Median lorlatinib-specific PFS was not reached versus 13.0 months (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.04\u20130.21; P&lt;0.001), and ORR was 92.7% versus 66.7% (P&lt;0.001). CNS-first progression occurred in 0 versus 19 patients; the 36-month cumulative incidence was 0% versus 43.9% (Gray\u2019s test P&lt;0.001). Median OS from lorlatinib initiation was not reached versus 28.8 months (HR, 0.22; 95% CI, 0.09\u20130.53; P&lt;0.001). Lorlatinib-emergent TRAEs were mainly grade 1\u20132, and permanent discontinuation due to TRAEs was uncommon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Within this lorlatinib-treated cohort, 1L lorlatinib was associated with more favorable lorlatinib-specific systemic, CNS, and survival outcomes than Post-2G lorlatinib. These findings are hypothesis-generating and do not constitute an all-comer comparison of complete first-line treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261480332","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:05:22Z","timestamp":1787234722000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lorlatinib-specific outcomes by timing of lorlatinib initiation in advanced ALK-positive non-small cell lung cancer: A retrospective cohort study"],"prefix":"10.1177","volume":"18","author":[{"given":"Ruiqi","family":"Song","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Hospital"},{"name":"Department of Medical Thoracic Oncology, Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer 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