Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: Updated survival results from a phase II trial (DESTINY-Breast01) Journal Article


Authors: Saura, C.; Modi, S.; Krop, I.; Park, Y. H.; Kim, S. B.; Tamura, K.; Iwata, H.; Tsurutani, J.; Sohn, J.; Mathias, E.; Liu, Y.; Cathcart, J.; Singh, J.; Yamashita, T.
Article Title: Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: Updated survival results from a phase II trial (DESTINY-Breast01)
Abstract: Background: Primary analysis of the multicenter, open-label, single-arm, phase II DESTINY-Breast01 trial (median follow-up 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with a median follow-up of 26.5 months (data cut-off 26 March 2021). Patients and methods: Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety. Results: The ORR by ICR was 62.0% [95% confidence interval (CI) 54.5% to 69.0%] in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) and 18.2 months (95% CI 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had one or more grade ≥3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n = 29), of which 2.7% (n = 5) were grade 5. Conclusions: These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC. © 2023 The Authors
Keywords: adult; cancer survival; treatment response; aged; major clinical study; overall survival; genetics; clinical trial; drug efficacy; drug safety; drug withdrawal; outcome assessment; metabolism; progression free survival; phase 2 clinical trial; tumor volume; gastrointestinal symptom; epidermal growth factor receptor 2; camptothecin; antineoplastic activity; breast neoplasms; monoclonal antibody; pneumonia; multicenter study; breast tumor; receptor, erbb-2; interstitial lung disease; trastuzumab; drug substitution; metastatic breast cancer; hematologic disease; adverse event; antibody conjugate; immunoconjugates; trastuzumab emtansine; refractory cancer; antibodies, monoclonal, humanized; human epidermal growth factor receptor 2 positive breast cancer; her2 positive; humans; human; female; article; ado-trastuzumab emtansine; treatment response time; trastuzumab deruxtecan
Journal Title: Annals of Oncology
Volume: 35
Issue: 3
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2024-03-01
Start Page: 302
End Page: 307
Language: English
DOI: 10.1016/j.annonc.2023.12.001
PUBMED: 38092229
PROVIDER: scopus
PMCID: PMC11322859
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Shanu Modi
    268 Modi