Results from the DESTINY-Breast12 Phase IIIb/IV trial reveal that Enhertu (trastuzumab deruxtecan) demonstrated significant overall and intracranial clinical activity in patients with HER2-positive metastatic breast cancer, including those with brain metastases who had undergone no more than two previous lines of therapy in the metastatic setting. The findings will be presented today as a late-breaking presentation (abstract #LBA18) at the European Society for Medical Oncology and published simultaneously in Nature Medicine.
Enhertu, a HER2-directed DXd antibody-drug conjugate (ADC), was discovered by Daiichi Sankyo and is being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Among patients with brain metastases at baseline, the primary endpoint of progression-free survival (PFS) by independent central review demonstrated a 12-month PFS rate of 61.6%. Additionally, the central nervous system (CNS) 12-month PFS rate was 58.9%. These results were consistent across patients with both stable and active brain metastases. For those with stable brain metastases, the 12-month PFS rate was 62.9%, and the CNS PFS rate was 57.8%. Patients with active brain metastases showed a 12-month PFS rate of 59.6% and a CNS PFS rate of 60.1%.
In patients without brain metastases at baseline, the primary endpoint of confirmed objective response rate (ORR) by independent review was 62.7%, including 23 complete responses (CR) and 128 partial responses (PR).
Dr. Nancy Lin, Associate Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and principal investigator of the trial, highlighted the significance of these findings: “Up to 50% of patients with HER2-positive metastatic breast cancer experience brain metastases, which impacts quality of life and outcomes. These data further characterize the clinical benefit and safety profile of Enhertu in these patients, which will help guide treatment decisions.”
Sunil Verma, Global Head of the Oncology Franchise at AstraZeneca, emphasized the results in patients with and without brain metastases, stating that the findings reinforce Enhertu’s role in second-line treatment for HER2-positive metastatic breast cancer.
Mark Rutstein, Global Head of Oncology Development at Daiichi Sankyo, added, “Treating brain metastases in breast cancer is challenging due to limited effective options. These results show that Enhertu provides strong clinical activity, both overall and intracranially, supporting its potential role for patients with active or stable brain metastases.”
A post-hoc analysis of patients with active brain metastases revealed a CNS ORR of 82.6% (19 out of 23 patients) for those without prior local CNS therapy and 50.0% (19 out of 38 patients) for those who had progressed following prior local CNS treatment.
The safety profile of Enhertu in the DESTINY-Breast12 trial was consistent with previous studies, with no new safety concerns identified. Among patients without brain metastases, 12.9% experienced interstitial lung disease (ILD) or pneumonitis, compared to 16.0% of patients with brain metastases. Most ILD events were low grade (Grade 1 or 2), though there were Grade 5 events in both cohorts, including five fatal cases of ILD or pneumonitis in the brain metastases group.
Enhertu is currently approved in over 65 countries for the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have previously received an anti-HER2-based therapy.
