{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T18:56:39Z","timestamp":1794336999441,"version":"4.9.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"The Science and Technology Agency of Qinghai Province","award":["2022-ZJ-719"],"award-info":[{"award-number":["2022-ZJ-719"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Science Progress"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study evaluated the hepatotoxicity risk of anaplastic lymphoma kinase (\n                      <jats:italic toggle=\"yes\">ALK)\/ROS1-<\/jats:italic>\n                      tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective analysis of 19,611 FAERS reports related to\n                      <jats:italic toggle=\"yes\">ALK\/ROS1<\/jats:italic>\n                      -TKIs (2011\u20132025) identified 1495 hepatotoxicity cases. Disproportionality analysis (reporting odds ratio, proportional reporting ratio, empirical Bayes geometric mean) assessed six\n                      <jats:italic toggle=\"yes\">ALK-<\/jats:italic>\n                      TKIs and three\n                      <jats:italic toggle=\"yes\">ROS1-<\/jats:italic>\n                      TKIs. Temporal trends, clinical outcomes, and differences across TKI generations were examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Second-generation\n                      <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                      -TKIs (e.g. alectinib) showed the most favorable hepatic safety profile, with the lowest observed mortality (3.5%) and hospitalization (13.0%). First-generation TKIs (crizotinib, ceritinib) and newer agents (lorlatinib, entrectinib) were associated with higher fatality rates (12.0%\u201313.2%). Most hepatotoxic events (51.9%) occurred within one month; however, 8.37% developed after one year. Mechanistically, the lower risk with second-generation TKIs may reflect less CYP-dependent metabolism and greater target selectivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Analysis of FAERS reports indicates substantial heterogeneity in hepatotoxicity risk among\n                      <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                      inhibitors. Second-generation agents showed lower mortality and hospitalization than first- and third-generation counterparts. Crizotinib, ceritinib, and lorlatinib were associated with notably high fatality rates, warranting continuous hepatic monitoring.\n                      <jats:italic toggle=\"yes\">ROS1<\/jats:italic>\n                      inhibitors (e.g. entrectinib) may exhibit distinct hepatotoxicity profiles. These findings should be interpreted cautiously given inherent reporting biases. Future priorities include prospective studies, biomarker-integrated risk stratification, mechanistic investigation, and AI-enhanced monitoring to optimize the risk\u2013benefit profile of\n                      <jats:italic toggle=\"yes\">ALK\/ROS1<\/jats:italic>\n                      -TKIs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/00368504251387821","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:50:28Z","timestamp":1760550628000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatotoxicity of ALK\/ROS1 tyrosine kinase inhibitors in non-small cell lung cancer patients: A pharmacovigilance study based on signal mining and analysis of the FDA adverse event reporting system database"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1291-4788","authenticated-orcid":false,"given":"Weixing","family":"Zhao","sequence":"first","affiliation":[{"name":"Graduate School of Qinghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9117-0829","authenticated-orcid":false,"given":"Xiaoni","family":"Jin","sequence":"additional","affiliation":[{"name":"Graduate School of Qinghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8186-6649","authenticated-orcid":false,"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Graduate School of Qinghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6669-493X","authenticated-orcid":false,"given":"Huiyuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Graduate School of Qinghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6248-6179","authenticated-orcid":false,"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Qinghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.6993"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0408-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.08.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30655-2"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.5587"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61030490"},{"key":"e_1_3_4_9_2","first-page":"1582","article-title":"First-line Crizotinib versus chemotherapy in ALK-positive lung cancer","volume":"373","year":"2015","unstructured":"First-line Crizotinib versus chemotherapy in ALK-positive lung cancer. 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