{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:53Z","timestamp":1788844253672,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carmelina Ratto and Carlo Capra"},{"DOI":"10.13039\/501100005010","name":"Fondazione AIRC per la Ricerca sul Cancro","doi-asserted-by":"crossref","award":["IG 2024\u2014ID30919"],"award-info":[{"award-number":["IG 2024\u2014ID30919"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Purpose: Trastuzumab deruxtecan (T-DXd) has significantly improved outcomes in patients with HER2-positive and HER2-low\/ultralow metastatic breast cancer (MBC). However, most patients eventually discontinue treatment. In clinical trials, discontinuation without disease progression occurred in 30\u201360% of cases, but real-world data on the reasons for discontinuation and subsequent treatment strategies remain limited. This study aimed to describe T-DXd discontinuation patterns and post-discontinuation treatments in a real-world setting. Methods: We conducted a single-center retrospective observational study including consecutive patients with MBC treated with T-DXd between July 2018 and December 2025. Patients who discontinued T-DXd for any reason were included. Reasons for discontinuation, treatment duration, response outcomes, and subsequent systemic therapies were analyzed using descriptive statistics. Results: Overall, 93 patients were included: 71.0% had HER2-positive, 26.9% HER2-low, and 2.1% HER2 0 tumors. The primary reason for discontinuation was progressive disease (82.8%). Other reasons included adverse events (14.0%), non-treatment-related causes (2.2%) and patient decision (1.1%). Interstitial lung disease represented the most common toxicity leading to discontinuation (10.8%). The median treatment duration was 7.9 months overall and was longer in patients with HER2-positive than in thosewith HER2-low and HER2 0 disease. Among evaluable patients, overall response rate was 83.1% in HER2-positive tumors and 52% in HER2-low tumors. After discontinuation, 80.6% of patients received subsequent therapy. Patients discontinuing for reasons other than progression had longer treatment exposure. Conclusions: In this real-world cohort, most T-DXd discontinuations were due to disease progression, while adverse event-related discontinuations were less frequent than in clinical trials. Several factors may influence treatment persistence, including toxicity management. Further evaluation in larger, multicenter cohorts is warranted to better characterize their contribution.<\/jats:p>","DOI":"10.3390\/cancers18172882","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low Rates of Discontinuation Unrelated to Disease Progression with Trastuzumab Deruxtecan in Metastatic Breast Cancer: A Real-World Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-3585","authenticated-orcid":false,"given":"Luca","family":"Licata","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4843-7811","authenticated-orcid":false,"given":"Francesca","family":"Patan\u00e8","sequence":"additional","affiliation":[{"name":"Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Guarino","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-421X","authenticated-orcid":false,"given":"Barbara","family":"Galbardi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0271-2158","authenticated-orcid":false,"given":"Annarita","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7444-8578","authenticated-orcid":false,"given":"Marco","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Yale School of Medicine, Yale Cancer Center, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Zanibelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8379-1497","authenticated-orcid":false,"given":"Giulia","family":"Notini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-2884","authenticated-orcid":false,"given":"Matteo Maria","family":"Naldini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Bosi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Radiation Oncology, New York-Presbyterian\/Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5163-6021","authenticated-orcid":false,"given":"Antonella","family":"Chiavassa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Santa Croce e Carle Hospital, 12100 Cuneo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Piras","sequence":"additional","affiliation":[{"name":"Division of Medical Senology, IEO European Institute of Oncology, IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Persano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Rognone","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Sica","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Zambelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Zucchinelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-6267","authenticated-orcid":false,"given":"Giampaolo","family":"Bianchini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1158\/1078-0432.CCR-15-2822","article-title":"DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1","volume":"22","author":"Ogitani","year":"2016","journal-title":"Clin. 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Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S334","DOI":"10.1016\/j.annonc.2023.09.553","article-title":"376O Trastuzumab deruxtecan (T-DXd) versus treatment of physician\u2019s choice (TPC) in patients (pts) with HER2-low unresectable and\/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study","volume":"34","author":"Modi","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMoa2407086","article-title":"Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer","volume":"391","author":"Bardia","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_9","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. 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Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2882\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:30:02Z","timestamp":1788841802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":30,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172882"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172882","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}