{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:03Z","timestamp":1788783123012,"version":"build-2803163510"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with anaplastic lymphoma kinase (ALK)-positive malignancies increasingly rely on ALK inhibitors (ALKis) as first-line therapy, yet thromboembolism (TE) across the ALKi family and its impact on patients\u2019 safety remain incompletely characterized, particularly in the real-world populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to evaluate the real-world TE risks associated with ALKis using pharmacovigilance data mining and to identify and characterize the high-risk contributors to TE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We extracted 52,808 adverse event (AE) reports from the FDA Adverse Event Reporting System (2013\u20132024), including 17,124 ALKi-treated patients. TE signal strength was calculated via disproportionality analysis and presented by the lower limit of reporting odds ratio (ROR\n                      <jats:sub>025<\/jats:sub>\n                      ) and information component (IC\n                      <jats:sub>025<\/jats:sub>\n                      ). Multivariate logistic regression and time-to-onset (TTO) analyses were conducted to characterize the risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among ALKi users, 251\u00a0TE cases were identified. Crizotinib exhibited significant TE safety signals for embolism (ROR\n                      <jats:sub>025<\/jats:sub>\n                      = 2.66; IC0\n                      <jats:sub>25<\/jats:sub>\n                      = 1.19), pulmonary artery thrombosis (ROR\n                      <jats:sub>025<\/jats:sub>\n                      = 4.94; IC0\n                      <jats:sub>25<\/jats:sub>\n                      = 1.01), pulmonary thrombosis (ROR\n                      <jats:sub>025<\/jats:sub>\n                      = 1.29; IC0\n                      <jats:sub>25<\/jats:sub>\n                      = 0.13), and venous thrombosis limb (ROR\n                      <jats:sub>025<\/jats:sub>\n                      = 1.66; IC0\n                      <jats:sub>25<\/jats:sub>\n                      = 0.08). Older age (OR = 1.006, P = 2.40e-06), male sex (OR = 1.47, P = 2.00e-16), and crizotinib use (OR = 2.79, P = 1.59e-05) independently predicted fatal TE outcomes. Female patients &amp;lt;65 years experienced earlier TE onset (median 14 vs. 44\u201353 days; P = 0.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study validates the elevated TE safety signal strength of crizotinib in the real-world settings, while no disproportionate TE signals were detected for other ALKi in the FAERS database. Clinicians could prioritize agent-specific risks, especially in older male patients and during early treatment phases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1855116","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:31:36Z","timestamp":1788780696000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterogeneity of thromboembolic risk across ALK inhibitors: a retrospective real-world study identifying crizotinib-specific signals and high-risk subpopulations"],"prefix":"10.3389","volume":"17","author":[{"given":"Rong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics","place":["Fuzhou, China"]},{"name":"Department of Hematology\/Oncology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics","place":["Fuzhou, China"]},{"name":"Department of Pediatrics, The Chinese University of","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fonc.2025.1566816","article-title":"Treatment of metastatic ALK-positive non-small cell lung cancer: indirect comparison of different ALK inhibitors using reconstructed patient data","volume":"15","author":"Damuzzo","year":"2025","journal-title":"Front. 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