{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:25:24Z","timestamp":1791487524975,"version":"4.3.4"},"reference-count":41,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020124","name":"Seagen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020124","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinical-breast-cancer.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Breast Cancer"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.clbc.2026.05.010","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:52:53Z","timestamp":1783677173000},"page":"21-30","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tucatinib in Combination With Trastuzumab Deruxtecan in Patients With Previously Treated HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer: An Open-Label Phase 2 Study"],"prefix":"10.1016","volume":"26","author":[{"given":"Shanu","family":"Modi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi K.","family":"Murthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Jo","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy U.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"McAndrew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Specht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia B.","family":"Zelnak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diqiong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet K.","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika P.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.clbc.2026.05.010_bib0001","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.3390\/cancers15102664","article-title":"HER2 intratumoral heterogeneity in breast cancer, an evolving concept","volume":"15","author":"Hou","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.clbc.2026.05.010_bib0002","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1016\/S0140-6736(16)32417-5","article-title":"HER2-positive breast cancer","volume":"389","author":"Loibl","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.clbc.2026.05.010_bib0003","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJMoa1113216","article-title":"Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer","volume":"366","author":"Baselga","year":"2012","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0004","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S1470-2045(13)70130-X","article-title":"Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study","volume":"14","author":"Swain","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0005","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.breast.2014.06.009","article-title":"Metastatic breast cancer subtypes and central nervous system metastases","volume":"23","author":"Aversa","year":"2014","journal-title":"Breast"},{"key":"10.1016\/j.clbc.2026.05.010_bib0006","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11912-019-0802-6","article-title":"Systemic therapy of central nervous system metastases of breast cancer","volume":"21","author":"Leone","year":"2019","journal-title":"Curr Oncol Rep"},{"key":"10.1016\/j.clbc.2026.05.010_bib0007","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41523-023-00584-5","article-title":"Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and\/or leptomeningeal disease (ROSET-BM)","volume":"9","author":"Niikura","year":"2023","journal-title":"NPJ Breast Cancer"},{"key":"10.1016\/j.clbc.2026.05.010_bib0008","article-title":"HER2-positive breast cancer brain metastasis: a new and exciting landscape","volume":"5","author":"Zimmer","year":"2022","journal-title":"Cancer Rep (Hoboken)"},{"key":"10.1016\/j.clbc.2026.05.010_bib0009","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/cancers16010023","article-title":"Systemic therapies for HER2-positive advanced breast cancer","volume":"16","author":"Angelis","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.clbc.2026.05.010_bib0010","doi-asserted-by":"crossref","first-page":"e957","DOI":"10.1093\/oncolo\/oyae055","article-title":"Optimal sequential strategies for antibody-drug conjugate in metastatic breast cancer: evaluating efficacy and cross-resistance","volume":"29","author":"Chen","year":"2024","journal-title":"Oncologist"},{"key":"10.1016\/j.clbc.2026.05.010_bib0011","article-title":"Decoding clinical trials in metastatic breast cancer: practical insights for optimal therapy sequencing","volume":"45","author":"Corti","year":"2025","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"10.1016\/j.clbc.2026.05.010_bib0012","first-page":"2103","article-title":"Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer","volume":"9","author":"Xuhong","year":"2019","journal-title":"Am J Cancer Res"},{"key":"10.1016\/j.clbc.2026.05.010_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.breast.2024.103756","article-title":"6th and 7th international consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)","volume":"76","author":"Cardoso","year":"2024","journal-title":"Breast"},{"key":"10.1016\/j.clbc.2026.05.010_bib0014","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.annonc.2021.09.019","article-title":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","volume":"32","author":"Gennari","year":"2021","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0015","doi-asserted-by":"crossref","first-page":"594","DOI":"10.6004\/jnccn.2023.0031","article-title":"NCCN Guidelines(R) insights: breast cancer, version 4.2023","volume":"21","author":"Gradishar","year":"2023","journal-title":"J Natl Compr Canc Netw"},{"key":"10.1016\/j.clbc.2026.05.010_bib0016","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1470-2045(19)30863-0","article-title":"Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study","volume":"21","author":"Swain","year":"2020","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0017","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1056\/NEJMoa2508668","article-title":"Trastuzumab deruxtecan plus pertuzumab for HER2-positive metastatic breast cancer","volume":"394","author":"Tolaney","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clbc.2026.05.010_sbref0018","series-title":"FDA approves fam-trastuzumab deruxtecan-nxki with pertuzumab for unresectable or metastatic HER2-positive breast cancer","year":"2025"},{"key":"10.1016\/j.clbc.2026.05.010_bib0019","first-page":"GS2","volume":"31","author":"Metzger","year":"2025","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.clbc.2026.05.010_sbref0020","series-title":"TUKYSA combination significantly improves progression-free survival as first-line maintenance in HER2+ metastatic breast cancer in HER2CLIMB-05 trial","year":"2025"},{"key":"10.1016\/j.clbc.2026.05.010_bib0021","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1038\/s41591-024-03021-7","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial","volume":"30","author":"Cortes","year":"2024","journal-title":"Nat Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0022","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1056\/NEJMoa2115022","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer","volume":"386","author":"Cortes","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0023","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0140-6736(22)02420-5","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial","volume":"401","author":"Hurvitz","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.clbc.2026.05.010_bib0024","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1056\/NEJMoa1914609","article-title":"Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer","volume":"382","author":"Murthy","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0025","article-title":"First line therapy for HER2+ MBC: A new treatment paradigm?","volume":"43","author":"Isaacs","year":"2025","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0026","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.ejmech.2017.10.021","article-title":"Dual or multi-targeting inhibitors: the next generation anticancer agents","volume":"143","author":"Raghavendra","year":"2018","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.clbc.2026.05.010_bib0027","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1158\/1535-7163.MCT-19-0873","article-title":"Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models","volume":"19","author":"Kulukian","year":"2020","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.clbc.2026.05.010_bib0028","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.SABCS19-P1-18-09","article-title":"Tucatinib, a HER2-selective tyrosine kinase inhibitor, increases the anti-tumor activity of trastuzumab antibody-drug conjugates in preclinical models of HER2+ breast cancer","volume":"80","author":"Kulukian","year":"2020","journal-title":"Cancer Res"},{"key":"10.1016\/j.clbc.2026.05.010_bib0029","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1158\/2767-9764.CRC-23-0302","article-title":"HER2-selective and reversible tyrosine kinase inhibitor tucatinib potentiates the activity of T-DM1 in preclinical models of HER2-positive breast cancer","volume":"3","author":"Olson","year":"2023","journal-title":"Cancer Res Commun"},{"key":"10.1016\/j.clbc.2026.05.010_bib0030","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.annonc.2024.08.2347","article-title":"A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases","volume":"35","author":"Andre","year":"2024","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0031","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1038\/s41591-024-03261-7","article-title":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b\/4 trial","volume":"30","author":"Harbeck","year":"2024","journal-title":"Nat Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0032","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/jamaoncol.2022.5610","article-title":"Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial","volume":"9","author":"Lin","year":"2023","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0033","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.annonc.2025.11.005","article-title":"Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02","volume":"37","author":"Hurvitz","year":"2025","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0034","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1056\/NEJMoa1914510","article-title":"Trastuzumab deruxtecan in previously treated HER2-positive breast cancer","volume":"382","author":"Modi","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clbc.2026.05.010_bib0035","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(23)00725-0","article-title":"Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial","volume":"401","author":"Andre","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.clbc.2026.05.010_bib0036","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.annonc.2023.12.001","article-title":"Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01)","volume":"35","author":"Saura","year":"2024","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0037","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.102924","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial","volume":"9","author":"Hurvitz","year":"2024","journal-title":"ESMO Open"},{"key":"10.1016\/j.clbc.2026.05.010_bib0038","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/s41416-023-02426-4","article-title":"Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level","volume":"129","author":"Atallah","year":"2023","journal-title":"Br J Cancer"},{"key":"10.1016\/j.clbc.2026.05.010_bib0039","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/JCMA.0000000000000883","article-title":"Impacts of HER2 immunohistochemical scores on response and outcomes of HER2-positive breast cancers after neoadjuvant therapy","volume":"86","author":"Chiu","year":"2023","journal-title":"J Chin Med Assoc"},{"key":"10.1016\/j.clbc.2026.05.010_bib0040","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5306\/wjco.v15.i1.5","article-title":"Prognostic factors of breast cancer brain metastasis","volume":"15","author":"Yakar","year":"2024","journal-title":"World J Clin Oncol"},{"key":"10.1016\/j.clbc.2026.05.010_bib0041","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1001\/jamaoncol.2018.1812","article-title":"Tucatinib combined with ado-trastuzumab emtansine in advanced ERBB2\/HER2-positive metastatic breast cancer: a phase 1b clinical trial","volume":"4","author":"Borges","year":"2018","journal-title":"JAMA Oncol"}],"container-title":["Clinical Breast Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1526820926000832?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1526820926000832?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T23:31:55Z","timestamp":1786145515000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1526820926000832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S1526820926000832"],"URL":"https:\/\/doi.org\/10.1016\/j.clbc.2026.05.010","relation":{},"ISSN":["1526-8209"],"issn-type":[{"value":"1526-8209","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tucatinib in Combination With Trastuzumab Deruxtecan in Patients With Previously Treated HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer: An Open-Label Phase 2 Study","name":"articletitle","label":"Article Title"},{"value":"Clinical Breast Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clbc.2026.05.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}