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• W4381431796 abstract "Recently, trastuzumab deruxtecan (T-DXd) has emerged as a transformative therapy for the treatment of HER2-expressing metastatic breast cancer (mBC). 1 Modi S. Saura C. Yamashita T. et al. Abstract PD3-06: Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer. Cancer Res. 2021; 81 (PD3-06) Google Scholar , 2 André F, Park YH, Kim SB, et al. 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. Lancet [Internet]. 2023. Available at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00725-0/fulltext. Cited April 30, 2023. Google Scholar , 3 Modi S. Jacot W. Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022; 387: 9-20 Crossref PubMed Scopus (360) Google Scholar Over several years, the standard treatment of patients with HER2-positive mBC progressing on anti-HER2 antibodies and taxanes was trastuzumab emtansine (T-DM1). 4 Cardoso F. Paluch-Shimon S. Senkus E. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020; 31: 1623-1649 Abstract Full Text Full Text PDF PubMed Scopus (554) Google Scholar ,5 Verma S. Miles D. Gianni L. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012; 367: 1783-1791 Crossref PubMed Scopus (2699) Google Scholar In 2022, T-DXd obtained regulatory approval in patients with HER2-positive unresectable or mBC who have previously received an anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant/adjuvant setting, and experienced disease recurrence during or within 6 months of completing therapy. 6 FDA D.I.S.C.O. Burst Edition: FDA approval of Enhertu (fam-trastuzumab deruxtecan-nxki) for adult patients with unresectable or metastatic HER2-positive breast cancer. FDA [Internet]. 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-enhertu-fam-trastuzumab-deruxtecan-nxki-adult-patients Google Scholar ,7 European Medicines Agency Recommends T-DXd for approval in European Union in Advanced HER2+ Breast Cancer [Internet]. Cancer Netw. 2022. Available at https://www.cancernetwork.com/view/european-medicines-agency-recommends-t-dxd-for-approval-in-european-union-in-advanced-her2-breast-cancer. Cited March 19, 2023. Google Scholar The approval was based on DESTINY-Breast03 trial, a randomized phase III study that showed the superiority of T-DXd versus T-DM1 in 524 patients with HER2-positive mBC previously treated with trastuzumab and a taxane. T-DXd reduced the risk of progression or death by 72% [hazard ratio (HR): 0.28, 95% confidence interval (CI) 0.22-0.37, P < 0.001], with a median progression-free survival (PFS) not reached [95% CI 18.5-not reached (NR)] versus 6.8 months (95% CI 5.6-8.2 months), as assessed by blinded independent central review. 8 Cortés J. Kim S.B. Chung W.P. et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022; 386: 1143-1154 Crossref PubMed Scopus (232) Google Scholar An updated analysis of DESTINY-Breast03 reported a median overall survival (OS) not reached (95% CI 40.5-NR) with T-DXd and not reached (34.0-NR) with T-DM1 (HR: 0.64, 95% CI 0.47-0.87, P = 0·0037). 9 Hurvitz S.A. Hegg R. Chung W.-P. et al. Abstract GS2-02: Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results of the randomized, phase 3 study DESTINY-Breast03. Cancer Res. 2023; 83 (GS2-02) Google Scholar On the other hand, when we look at the safety outcomes, discontinuation of treatment due to adverse events (AEs) and the incidence of drug-related AEs of any grade were higher with T-DXd as compared to T-DM1 (13.6% versus 7.3% and 98.1% versus 86.6%, respectively). The most commonly drug-related AEs of any grade reported with T-DXd were nausea (72.8% versus 27.6%), fatigue (44.7% versus 29.5%), and vomiting (44.0% versus 5.7%), all favoring T-DM1. Furthermore, interstitial lung disease (ILD) or pneumonitis was identified in 10.5% of cases with T-DXd and 1.9% with T-DM1. 8 Cortés J. Kim S.B. Chung W.P. et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022; 386: 1143-1154 Crossref PubMed Scopus (232) Google Scholar" @default.
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• W4381431796 title "Trastuzumab deruxtecan for breast cancer: do patients experience a comprehensive benefit?" @default.
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