Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial

Cort&#233;s, J; Hurvitz, SA; Im, SA; Iwata, H; Curigliano, G; Kim, SB; Chiu, JWY; Pedrini, JL; Li, W; Yonemori, K; Bianchini, G; Loi, S; Borges, GS; Wang, X; Bachelot, T; Nakatani, S; Ashfaque, S; Liang, Z; Egorov, A; Hamilton, E

Author(s): Cortés, J; Hurvitz, SA; Im, SA; Iwata, H; Curigliano, G; Kim, SB; Chiu, JWY; Pedrini, JL; Li, W; Yonemori, K; Bianchini, G; Loi, S; Borges, GS; Wang, X; Bachelot, T; Nakatani, S; Ashfaque, S; Liang, Z; Egorov, A; Hamilton, E;
Details: Publication Year 2024-08,Volume 30,Issue #8,Page 2208-2215
Journal Title: Nature Medicine
Publication Type: Research article
Abstract: Trastuzumab deruxtecan (T-DXd) demonstrated significantly improved efficacy over trastuzumab emtansine (T-DM1) in DESTINY-Breast03 (median follow-up, 28 months). We report updated efficacy and safety analyses, including secondary and exploratory efficacy endpoints (median follow-up, 41 months) of DESTINY-Breast03. Patients with advanced HER2-positive metastatic breast cancer previously treated with taxane and trastuzumab were randomized to T-DXd (5.4 mg per kg (261 patients)) or T-DM1 (3.6 mg per kg (263 patients)). The primary endpoint was progression-free survival (PFS) by blinded independent central review and was previously reported. The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate, duration of response and PFS (all by investigator assessment) and safety. At data cutoff, 20 November 2023, median PFS by investigator assessment was 29.0 versus 7.2 months (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.24-0.38), the 36-month PFS rate was 45.7% versus 12.4% and median OS was 52.6 versus 42.7 months (HR, 0.73; 95% CI, 0.56-0.94) with T-DXd versus T-DM1, respectively. Treatment-emergent adverse events were consistent with the previous analyses. No new instances of grade ≥3 interstitial lung disease or pneumonitis occurred (all grade rate, 16.7% (T-DXd) versus 3.4% (T-DM1)). With longer follow-up, T-DXd continued to demonstrate superior efficacy over T-DM1 with a manageable safety profile. ClinicalTrials.gov registration: NCT03529110 .
Publisher: Springer Nature
Keywords: Humans; *Breast Neoplasms/drug therapy/pathology/genetics/mortality; Female; *Trastuzumab/therapeutic use/adverse effects; *Receptor, ErbB-2/metabolism/genetics; *Ado-Trastuzumab Emtansine/therapeutic use/adverse effects; Middle Aged; Adult; Aged; Camptothecin/analogs & derivatives/therapeutic use/adverse effects; Neoplasm Metastasis; Immunoconjugates/therapeutic use/adverse effects; Progression-Free Survival; Survival Analysis; Antineoplastic Agents, Immunological/therapeutic use/adverse effects; Maytansine/analogs & derivatives/therapeutic use/adverse effects
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1038/s41591-024-03021-7
Open Access at Publisher's Site: https://doi.org/10.1038/s41591-024-03021-7
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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Last Modified: 2024-09-10 04:41:22