Enhertu achieved statistically significant overall survival, reducing risk of death by 36% vs. trastuzumab emtansine

Updated results from the DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. These results and primary results from the DESTINY-Breast02 Phase III trial will be presented today at the 2022 San Antonio Breast Cancer Symposium (SABCS), with the updated results from DESTINY-Breast03 simultaneously published in The Lancet.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

In the key secondary endpoint analysis of OS for DESTINY-Breast03, Enhertu demonstrated a 36% reduction in risk of death versus T-DM1 (based on a hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.47-0.87; p=0.0037). In both treatment arms, median OS was not yet reached (Enhertu [40.5-NE] versus T-DM1 [34.0-NE]) after a median duration of follow-up of 28.4 months for Enhertu and 26.5 months for T-DM1. An estimated 77.4% of patients were alive in the Enhertu arm at two years compared to 69.9% of patients treated with T-DM1. The observed survival benefit was consistent across all analysed subgroups, including patients with or without baseline brain metastases, with or without baseline visceral disease, those who were hormone receptor (HR)-positive or HR-negative, and regardless of prior pertuzumab or lines of systemic therapy.

Sara Hurvitz, MD, Medical Oncologist, Professor of Medicine, and Director of the Breast Cancer Clinical Trials Program in the Division of Hematology-Oncology at the David Geffen School of Medicine at UCLA, and Medical Director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA, said: “The main goals of therapy for advanced breast cancer are to control the disease and improve survival, and it is therefore critical to continue to improve upon existing treatment options, particularly in the metastatic setting. For patients with HER2-positive breast cancer who experience disease progression following initial treatment in the metastatic setting, Enhertu has shown significant improvement in survival compared to T-DM1, further confirming this medicine as the new standard of care.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The updated results for DESTINY-Breast03 showing that Enhertu extends patients’ lives and also delays progression by nearly two years reinforces our belief that this medicine has the potential to set a new standard of care for patients with HER2-positive metastatic breast cancer treated in the second-line setting. Complemented by DESTINY-Breast02, we now have two Phase III trials in HER2-positive metastatic breast cancer showing patients in these trials have more disease-free time and live longer when they receive Enhertu versus the previous standard of care.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The overall survival benefits shown in both the DESTINY-Breast03 and DESTINY-Breast02 trials further validate the role of Enhertu in potentially extending the lives of patients with previously treated HER2-positive breast cancer. Additionally, median progression-free survival was four times longer with one in five patients showing no detectable signs of disease when treated with Enhertu compared to T-DM1 in DESTINY-Breast03, which is particularly impressive in the metastatic setting of HER2-positive breast cancer.”

With the additional follow-up in DESTINY-Breast03, Enhertu also continued to demonstrate a clinically meaningful improvement in progression-free survival (PFS) with a 22 month improvement in median PFS over T-DM1, reaffirming the statistically significant finding at the previous interim analysis. The updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms. In this exploratory post-hoc analysis, the median PFS for patients in the Enhertu arm was 28.8 months compared to 6.8 months for T-DM1, as assessed by blinded independent central review (BICR). Confirmed objective response rate (ORR) was 78.5% in the Enhertu arm with 21.1% of patients demonstrating a complete response (CR) versus an ORR of 35.0% in the T-DM1 arm, where 9.5% of patients achieved a CR. The median duration of response (DoR) was 36.6 months in the Enhertu arm and 23.8 months in the T-DM1 arm.

Summary of updated results: DESTINY-Breast03

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