ENHERTU® shows strong clinical activity in HER2-positive metastatic breast cancer with brain metastases

Results from the DESTINY-Breast12 Phase IIIb/IV trial have revealed that ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrates significant overall and intracranial clinical activity in a large group of patients suffering from HER2-positive metastatic breast cancer with brain metastases. These findings are particularly notable among patients who had received no more than two previous lines of therapy in the metastatic setting. The results were presented at the European Society for Medical Oncology (ESMO24) and published simultaneously in Nature Medicine.

ENHERTU is a specifically engineered HER2-directed DXd antibody-drug conjugate (ADC) developed by Daiichi Sankyo and jointly commercialized by AstraZeneca and Daiichi Sankyo. The trial's primary endpoint for patients with brain metastases at the study's start was progression-free survival (PFS) by independent central review, showing a 12-month PFS rate of 61.6%. This was complemented by a central nervous system (CNS) 12-month PFS rate of 58.9%. The results were consistent for both stable and active brain metastases, with stable cases showing a 12-month PFS rate of 62.9% and a CNS PFS rate of 57.8%, and active cases showing a 12-month PFS rate of 59.6% and a CNS PFS rate of 60.1%.

For patients without brain metastases at baseline, the primary endpoint of confirmed objective response rate (ORR) by independent central review was 62.7%, including 23 complete responses (CR) and 128 partial responses (PR).

Dr. Nancy Lin of the Dana-Farber Cancer Institute, the principal investigator of the trial, noted that up to 50% of patients with HER2-positive metastatic breast cancer experience brain metastases, significantly impacting their quality of life and overall outcomes. The DESTINY-Breast12 data provide a clearer understanding of ENHERTU's clinical benefits and safety profile, assisting in guiding treatment decisions.

Sunil Verma, Global Head of the Oncology Franchise at AstraZeneca, emphasized that the trial's results underscore the clinical activity of ENHERTU for patients whose disease has metastasized to the brain. He added that the data reinforce confidence in ENHERTU as a second-line treatment for HER2-positive metastatic breast cancer.

Mark Rutstein, Global Head of Oncology Development at Daiichi Sankyo, highlighted the challenge of treating brain metastases in breast cancer patients due to limited effective options. He remarked that the results from DESTINY-Breast12 build on previous studies, showing ENHERTU's strong overall and intracranial clinical activity, thus supporting its potential role in treating both active and stable brain metastases.

A post-hoc analysis focusing on patients with active brain metastases indicated a CNS ORR of 82.6% for those who had not undergone prior local CNS therapy, compared to 50.0% for those who had experienced progression following previous local CNS therapy.

The safety profile of ENHERTU in the DESTINY-Breast12 trial was consistent with previous clinical trials for breast cancer, with no new safety concerns noted. Both cohorts, with and without brain metastases, generally reflected comparable safety profiles. Interstitial lung disease (ILD) or pneumonitis was observed in 12.9% of patients without brain metastases and 16.0% in patients with brain metastases, mostly of low grade (Grade 1 or 2). Grade 5 ILD events were reported in 1.2% of patients without brain metastases and 2.3% of patients with brain metastases.

ENHERTU has been approved in over 65 countries for the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have received prior anti-HER2-based therapy.