Enhertu showed substantial clinical activity in patients with HER2-positive metastatic breast cancer and brain metastases in DESTINY-Breast 12 trial

Results will be presented as a late-breaking presentation (abstract #LBA18) at the European Society for Medical Oncology and simultaneously published in Nature Medicine.

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

In patients with brain metastases at baseline, the primary endpoint of progression-free survival (PFS) by independent central review showed a 12-month PFS rate of 61.6%. Additionally, patients with brain metastases showed a central nervous system (CNS) 12-month PFS rate of 58.9%. Results were consistent in patients with stable and active brain metastases. Patients with stable brain metastases had a 12-month PFS rate of 62.9% and a 12-month CNS PFS rate of 57.8%. Patients with active brain metastases had a 12-month PFS rate of 59.6% and a 12-month CNS PFS rate of 60.1%.

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

Nancy Lin, MD, Associate Chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, MA, US and principal investigator for the trial, said: “Up to fifty per cent of patients with HER2-positive metastatic breast cancer experience the spread of disease to the brain during the course of their illness, which significantly impacts quality of life and outcomes. These data help further characterise the clinical benefit and safety profile of Enhertu in these patients, which will help guide treatment decisions.”

Mark Rutstein, Global Head, Oncology Development, Daiichi Sankyo, said: “Treating brain metastases in patients with breast cancer is challenging as there are few effective treatment options. Building on previous studies, these results show Enhertu can provide strong overall and intracranial clinical activity and support its potential role in treating patients with active or stable brain metastases.”  

DESTINY-Breast12; DESTINY-Breast12 is an open-label, multicentre, Phase IIIb/IV 2-cohort, non-comparative clinical trial designed to evaluate the efficacy and safety of Enhertu (5.4 mg/kg) in patients with previously treated advanced/metastatic HER2-positive breast cancer. The study includes patients without brain metastases (cohort 1) or with brain metastases (cohort 2) who have experienced disease progression following prior anti-HER2-based regimens and have received no more than two lines of therapy in the metastatic setting. Patients were enrolled into one of two cohorts according to the presence or absence of brain metastases at baseline. The primary endpoint of cohort 1 was ORR as assessed by independent review (non-brain metastases cohort) and the primary endpoint of cohort 2 (brain metastases cohort) was PFS. Additional endpoints included CNS PFS, CNS ORR, ORR in the brain metastases cohort and safety. DESTINY-Breast12 enrolled 504 patients across multiple sites in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.
Citation; Published: 13 September 2024, Harbeck, N., Ciruelos, E., Jerusalem, G. et al. "Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase IIIb/IV trial". Nat Med (2024). https://doi.org/10.1038/s41591-024-03261-7 Nature Medicine (2024).