Results from the DESTINY-Breast12 phase 3b/4 trial reveal that ENHERTU® (trastuzumab deruxtecan) demonstrated significant clinical activity in HER2-positive metastatic breast cancer patients with brain metastases who had received up to two prior lines of therapy. These findings will be presented today as a late-breaking paper (LBA18) at the European Society for Medical Oncology (#ESMO24) and published simultaneously in Nature Medicine.
ENHERTU, an HER2-targeted DXd antibody drug conjugate developed by Daiichi Sankyo and AstraZeneca, showed a 12-month progression-free survival (PFS) rate of 61.6% (95% CI: 54.9-67.6) in patients with brain metastases at baseline (n=263). The central nervous system (CNS) 12-month PFS rate was 58.9% (95% CI: 51.9-65.3). Results were consistent across patients with stable (n=157) and active (n=106) brain metastases.
In patients without brain metastases at baseline (n=241), ENHERTU achieved a confirmed objective response rate (ORR) of 62.7% (95% CI: 56.5-68.8), including 23 complete responses and 128 partial responses. For patients with brain metastases, the CNS ORR was 62.3% (95% CI: 50.1-74.5) in those with active metastases and 79.2% (95% CI: 70.2-88.3) in those with stable metastases.
The safety profile of ENHERTU in DESTINY-Breast12 was in line with previous trials, with common grade 3 or higher adverse events including neutropenia (16% in brain metastases and 18% in non-brain metastases), fatigue (9% in brain metastases and 10% in non-brain metastases), anemia (7% in brain metastases and 5% in non-brain metastases), and nausea (5% in both groups). Interstitial lung disease (ILD) or pneumonitis occurred in 16.0% of patients with brain metastases and 12.9% of those without.
Nancy Lin, MD, Principal Investigator for the trial, noted, “Up to fifty percent of HER2-positive metastatic breast cancer patients develop brain metastases, impacting quality of life and outcomes. These data highlight ENHERTU’s clinical benefit and safety profile, guiding treatment decisions.”
Mark Rutstein, MD, Global Head of Oncology Clinical Development at Daiichi Sankyo, emphasized ENHERTU’s potential in treating brain metastases, while Sunil Verma, MD, Global Head of Oncology Franchise at AstraZeneca, expressed confidence in ENHERTU’s profile for second-line treatment of HER2-positive metastatic breast cancer.
DESTINY-Breast12, a phase 3b/4 trial, evaluated ENHERTU (5.4 mg/kg) in patients with advanced HER2-positive breast cancer. The study’s primary endpoints were PFS for patients with brain metastases and ORR for those without.
