ENHERTU® Demonstrates Significant Activity in HER2 Positive Metastatic Breast Cancer with Brain Metastases

Results from the DESTINY-Breast12 phase 3b/4 trial reveal that ENHERTU® (trastuzumab deruxtecan) has shown significant clinical benefits for patients with HER2 positive metastatic breast cancer, particularly those with brain metastases. The findings will be presented at the European Society for Medical Oncology (#ESMO24) and have been published in Nature Medicine.

ENHERTU, a HER2-directed DXd antibody drug conjugate (ADC) developed by Daiichi Sankyo in collaboration with AstraZeneca, was tested on patients with HER2 positive metastatic breast cancer who had brain metastases and had received no more than two prior lines of therapy. The primary endpoint analysis measured progression-free survival (PFS) and confirmed objective response rate (ORR).

In patients with brain metastases at baseline (263 participants), ENHERTU achieved a 12-month PFS rate of 61.6% (95% confidence interval [CI]: 54.9-67.6). For those with stable brain metastases (157 patients), the 12-month PFS rate was 62.9% (95% CI: 54.0-70.5), while those with active brain metastases (106 patients) had a 12-month PFS rate of 59.6% (95% CI: 49.0-68.7). For the central nervous system (CNS) specifically, the 12-month PFS rate was 58.9% (95% CI: 51.9-65.3), with 57.8% for stable brain metastases and 60.1% for active brain metastases.

In patients without brain metastases at baseline (241 participants), the ORR was 62.7% (95% CI: 56.5-68.8), with 23 complete responses and 128 partial responses. Additionally, ENHERTU displayed a CNS ORR of 62.3% (95% CI: 50.1-74.5) in patients with active brain metastases and 79.2% (95% CI: 70.2-88.3) in those with stable brain metastases.

According to Dr. Nancy Lin, Associate Chief, Division of Breast Oncology at Dana-Farber Cancer Institute and Principal Investigator for the trial, up to 50% of patients with HER2 positive metastatic breast cancer develop brain metastases during their illness, significantly affecting quality of life and outcomes. The data from this study will help inform treatment decisions by further clarifying the clinical benefits and safety profile of ENHERTU.

The safety profile of ENHERTU in the DESTINY-Breast12 trial was consistent with previous breast cancer trials. Adverse events of grade 3 or higher, occurring in 5% or more patients in either cohort, included neutropenia, fatigue, anemia, and nausea. Interstitial lung disease (ILD) or pneumonitis was seen in 16.0% of patients in the brain metastases cohort and 12.9% in the non-brain metastases cohort. These findings were in line with earlier studies on the drug.

Dr. Mark Rutstein, Global Head of Oncology Clinical Development at Daiichi Sankyo, emphasized the challenge of treating brain metastases in breast cancer patients, highlighting the importance of these findings. Dr. Sunil Verma, Global Head of Oncology Franchise at AstraZeneca, noted that the results reinforce the potential of ENHERTU in treating HER2 positive metastatic breast cancer, both with and without brain metastases.

Patients in the trial received no more than two prior lines of therapy in the metastatic setting, with a median follow-up duration of 15.4 months for the brain metastases cohort and 16.1 months for the non-brain metastases cohort. As of the data cut-off on February 8, 2024, 213 patients remained on treatment.

The DESTINY-Breast12 study is an open-label, multicenter trial evaluating the efficacy and safety of ENHERTU. It involved patients with or without baseline brain metastases who had progressed after prior anti-HER2-based regimens. The study enrolled 504 patients across multiple regions, including Asia, Europe, North America, and Oceania.