{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:11:04Z","timestamp":1779970264075,"version":"3.53.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dato\u2010DXd (datopotamab deruxtecan) is an anti\u2010TROP2 antibody\u2010drug conjugate developed for the treatment of unresectable or metastatic hormone receptor\u2010positive, human epidermal growth factor receptor 2\u2010negative breast cancer (HR+\/HER2\u2010BC) who have received prior endocrine\u2010based therapy and chemotherapy for unresectable or metastatic disease. Associations between Dato\u2010DXd or its payload DXd pharmacokinetics (PK) and various efficacy and safety endpoints were investigated in the current analysis. Exposure\u2010efficacy analysis was conducted in a total of 352 patients with HR+\/HER2\u2010BC who received Dato\u2010DXd at 6 mg\/kg every 3 weeks (Q3W). Area under the curve in cycle 1 (AUC1) was identified as a significant covariate of overall survival (OS), with higher Dato\u2010DXd exposure associated with longer OS. Progression\u2010free survival (PFS) showed a positive trend with higher exposure, though baseline tumor size emerged as a more significant predictor in multivariable analyses. Exposure\u2010safety analysis revealed correlations between higher Dato\u2010DXd or DXd PK metrics and increased risk of selected safety events, including stomatitis and ocular surface events. PopPK analysis showed that Dato\u2010DXd exposure increased with body weight, and implementing a capped dose of 540 mg for patients \u226590 kg helped normalize exposure across weight groups. Exposure\u2010safety analysis further supported that this approach may reduce the potential associated safety risks. These results support the recommended Dato\u2010DXd dosing regimen (6 mg\/kg Q3W with dose capping for patients \u226590 kg) and highlight its favorable benefit\u2010risk profile in patients with HR+\/HER2\u2010breast cancer.<\/jats:p>","DOI":"10.1002\/jcph.70188","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:56:55Z","timestamp":1776326215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure\u2010Response Analyses of Datopotamab Deruxtecan (Dato\u2010DXd) in Patients with Hormone Receptor (HR) Positive, Human Epidermal Growth Factor Receptor 2 (HER2)\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0945-6510","authenticated-orcid":false,"given":"Zoey","family":"Tang","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyoungSoo","family":"Lim","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelima","family":"Denduluri","sequence":"additional","affiliation":[{"name":"Clinical Development Oncology R&amp;D AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Rokutanda","sequence":"additional","affiliation":[{"name":"Clinical Development Oncology R&amp;D AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhuo","family":"Pan","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Daiichi Sankyo Inc.  Basking Ridge NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hong","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Daiichi Sankyo Inc.  Basking Ridge NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Ren","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Vajjah","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"National Cancer Institute S Epidemiology and End Results (SEER) Program.Cancer stat facts: female breast cancer. 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Paper presented at:American Conference on Pharmacometrics (ACoP13); November 6\u20139 2022;Aurora CO."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13058"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70493"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1996.10476664"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010019\u201009635\u20106"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1487062"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.70119"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad212"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201017\u20102386"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201024\u201001349"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201024\u201001544"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70188","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70188","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:54:57Z","timestamp":1779969297000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jcph.70188"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70188","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70188"}}