{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:51:36Z","timestamp":1788054696320,"version":"build-2784847793"},"reference-count":23,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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":[[2023,9]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The BELA and BFORE trials compared bosutinib starting doses of 500\u2009mg once daily (QD) and 400\u2009mg QD, respectively, with imatinib in adults with newly diagnosed chronic phase chronic myeloid leukemia (CP\u2010CML). The B1871048 trial evaluated bosutinib 400\u2009mg QD in Japanese patients with newly diagnosed CP\u2010CML.<\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n This analysis assessed the impact of a lower bosutinib starting dose on key efficacy and safety outcomes.<\/jats:p>\n <\/jats:sec>\n \n Materials & Methods<\/jats:title>\n A pharmacokinetic model was used to estimate metrics of bosutinib exposure, and logistic regression was used to investigate relationships with efficacy (cumulative major molecular response [MMR] and cumulative complete cytogenetic response [CCyR]) and safety outcomes (eight prespecified adverse events).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Totals of 573 and 574 patients were included in the efficacy and safety endpoint analyses, respectively. Cumulative MMR and CCyR were similar across studies. Log(\n C<\/jats:italic>\n trough<\/jats:sub>\n ) and log(\n C<\/jats:italic>\n avg<\/jats:sub>\n ) were significant predictors of MMR and CCyR, and the probability of achieving MMR or CCyR increased 1.3\u2010fold or 2.7\u2010fold for every 1 unit increase in log(\n C<\/jats:italic>\n trough<\/jats:sub>\n ) or log(\n C<\/jats:italic>\n avg<\/jats:sub>\n ), respectively. An exposure\u2013response relationship was identified between time\u2010to\u2010event and risk of diarrhea, nausea, and vomiting. Significant relationships were also observed between time\u2010to\u2010event and log(\n C<\/jats:italic>\n avg<\/jats:sub>\n ),\n C<\/jats:italic>\n trough<\/jats:sub>\n , and\n C<\/jats:italic>\n avg<\/jats:sub>\n with diarrhea, nausea, and vomiting, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n A bosutinib exposure\u2010response relationship with safety and efficacy was observed.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Compared with 500\u2009mg QD, a bosutinib starting dose of 400\u2009mg QD improved tolerability in some patients with newly diagnosed CP\u2010CML without compromising efficacy.\n ClinicalTrials.gov<\/jats:ext-link>\n identifiers: NCT00574873; NCT02130557; NCT03128411.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.6439","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T02:03:32Z","timestamp":1691546612000},"page":"17981-17992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Population modeling of bosutinib\n exposure\u2010response<\/scp>\n in patients with newly diagnosed chronic phase chronic myeloid leukemia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-2842","authenticated-orcid":false,"given":"May","family":"Garrett","sequence":"first","affiliation":[{"name":"Pfizer Oncology San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3603-474X","authenticated-orcid":false,"given":"Beverly","family":"Knight","sequence":"additional","affiliation":[{"name":"Pfizer Oncology San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge E.","family":"Cortes","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-1331","authenticated-orcid":false,"given":"Michael W.","family":"Deininger","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"375","article-title":"SKI\u2010606, a 4\u2010anilino\u20103\u2010quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice","volume":"63","author":"Golas JM","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1199"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-355594"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-513937"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-390120"},{"key":"e_1_2_13_7_1","unstructured":"BOSULIF\u00ae (bosutinib) [prescribing information]. Pfizer Inc2017."},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.7522"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.7162"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-020-02878-x"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2378"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-022-03435-4"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.06.001"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-012-1987-7"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.3724"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1566-2"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12618"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.36"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116475"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1200-7"},{"key":"e_1_2_13_21_1","first-page":"85","article-title":"Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure\u2010response analysis of a Phase III study","volume":"5","author":"Wang X","year":"2013","journal-title":"Clin Pharmacol"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01148-9"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2699"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1385-4"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.6439","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:05:09Z","timestamp":1786968309000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":23,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1002\/cam4.6439"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6439","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]},"assertion":[{"value":"2023-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}