Trastuzumab deruxtecan in previously treated HER2-positive breast cancer Journal Article


Authors: Modi, S.; Saura, C.; Yamashita, T.; Park, Y. H.; Kim, S. B.; Tamura, K.; Andre, F.; Iwata, H.; Ito, Y.; Tsurutani, J.; Sohn, J.; Denduluri, N.; Perrin, C.; Aogi, K.; Tokunaga, E.; Im, S. A.; Lee, K. S.; Hurvitz, S. A.; Cortes, J.; Lee, C.; Chen, S.; Zhang, L.; Shahidi, J.; Yver, A.; Krop, I.; for the DESTINY-Breast01 Investigators
Article Title: Trastuzumab deruxtecan in previously treated HER2-positive breast cancer
Abstract: BACKGROUND Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide- based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation. METHODS In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the diseasecontrol rate, clinical-benefit rate, duration of response and progression-free survival, and safety. RESULTS Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%). CONCLUSIONS Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring. © 2019 Massachusetts Medical Society.
Journal Title: New England Journal of Medicine
Volume: 382
Issue: 7
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2020-01-01
Start Page: 610
End Page: 621
Language: English
DOI: 10.1056/NEJMoa1914510
PUBMED: 31825192
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Shanu Modi
    168 Modi