{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:13:59Z","timestamp":1765728839381,"version":"3.40.5"},"reference-count":32,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>ROS1\u2010<\/jats:italic> and <jats:italic>ALK<\/jats:italic>\u2010rearranged advanced NSCLCs are associated with increased thromboembolic risk. We hypothesized that a prothrombotic phenotype offers an evolutionary advantage to subsets of these cancers. The impact of this phenotype could alter outcomes from targeted therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a retrospective analysis of <jats:italic>ROS1\u2010<\/jats:italic> and <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLCs treated with crizotinib in a phase 1 trial, we compared progression\u2010free survival (PFS) and objective response rate (ORR) based on the history of anticoagulation use (a possible surrogate of thromboembolism) at baseline (within 90\u2009days before study enrollment) or within 90\u2009days of study treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve out of 53 (22.6%) <jats:italic>ROS1\u2010<\/jats:italic> and 39 out of 153 (25.5%) <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLCs received anticoagulation before or during the trial. Most <jats:italic>ROS1<\/jats:italic> and <jats:italic>ALK<\/jats:italic> patients on anticoagulation received low\u2010molecular\u2010weight heparin (75% and 64.1%, respectively). In the <jats:italic>ROS1<\/jats:italic>\u2010rearranged group, the median PFS (95% CI) values were 5.1 (4.4\u201314.4) and 29.0 (16.5\u201348.8) months, and the ORR values were 41.7% (95% CI: 15.2 to 72.3) and 80.5% (95% CI: 65.1 to 91.2) among those with and without anticoagulation treatment, respectively. In the <jats:italic>ALK<\/jats:italic>\u2010rearranged group, the median PFS (95% CI) was 7.1 (5.4\u20137.7) and 12.0 (9.4\u201318.3) months, and the ORR was 41% (95% CI: 25.6 to 57.9) and 74.3% (95% CI: 65.3 to 82.1) among those with and without anticoagulation, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Anticoagulation (as a potential surrogate of a prothrombotic subset) in <jats:italic>ROS1\u2010<\/jats:italic> and <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLCs may be associated with a lower PFS and ORR to crizotinib.<\/jats:p><jats:p>ClinicalTrial.gov: NCT00585195.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4789","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T10:54:44Z","timestamp":1651748084000},"page":"4422-4429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of anticoagulant use with clinical outcomes from crizotinib in <i>ALK<\/i><scp><i>\u2010<\/i><\/scp> and <i>ROS1<\/i>\u2010rearranged advanced non\u2010small cell lung cancers: A retrospective analysis of <scp>PROFILE<\/scp> 1001"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-3137","authenticated-orcid":false,"given":"Terry L.","family":"Ng","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C. C.","family":"Tsui","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry","family":"Wang","sequence":"additional","affiliation":[{"name":"Pfizer Oncology  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Usari","sequence":"additional","affiliation":[{"name":"Pfizer  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tejas","family":"Patil","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Wilner","sequence":"additional","affiliation":[{"name":"Pfizer Oncology  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Camidge","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.12.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2016.10.007"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02431-2017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.04.033"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.12.009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2019.06.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2020.01.017"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-942759"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.01.053"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08922.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.11.024"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.7199"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2350"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742999"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-720714"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13181"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-933341"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0371"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2008.12.009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70344-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz131"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.4584"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1145255"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704855200"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.395.2.7"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.002"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1079254"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.4794"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214886"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097\u20100142(19940701)74:1<38::aid\u2010cncr2820740108>3.0.co;2\u2010e"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00871.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22892"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4789","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T07:03:14Z","timestamp":1720076594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":32,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/cam4.4789"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4789","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"type":"print","value":"2045-7634"},{"type":"electronic","value":"2045-7634"}],"subject":[],"published":{"date-parts":[[2022,5,5]]},"assertion":[{"value":"2021-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}