Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial
Shanu Modi, William Jacot, Hiroji Iwata, Yeon Hee Park, María Vidal, Wei Li, Junji Tsurutani, Naoto T. Ueno, Khalil Zaman, Aleix Prat, Konstantinos Papazisis, Hope S. Rugo, Toshinari Yamashita, Nadia Harbeck, Seock‐Ah Im, Michelino De Laurentiis, Jean‐Yves Pierga, Xiaojia Wang, Andrea Gombos, Eriko Tokunaga, Cecilia Orbegoso Aguilar, Lotus Yung, Feng Xiao, Yingkai Cheng, David Cameron
Abstract
In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician’s choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55–0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55–0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%–10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 . This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.