Data from the phase 3b/4 DESTINY-Breast12 trial indicates that Enhertu (fam-trastuzumab deruxtecan-nxki) preserves health-related quality of life (HRQOL) and neurological function in patients with HER2-positive metastatic breast cancer, irrespective of the presence of brain metastases. The findings, presented at the 2024 San Antonio Breast Cancer Symposium, suggest that Enhertu's efficacy extends to maintaining patient well-being throughout treatment.
The DESTINY-Breast12 trial (NCT04739761) was an open-label study that examined Enhertu in adult patients with HER2-positive metastatic breast cancer with or without baseline brain metastases. Patients were administered intravenous Enhertu at a dose of 5.4 mg/kg every three weeks. The primary endpoint for the brain metastases cohort was progression-free survival (PFS), while the primary endpoint for the non-brain metastases cohort was objective response rate (ORR).
Key Findings on Quality of Life
At the data cutoff of February 8, 2024, the estimated 12-month deterioration-free rate in terms of global health status (GHS)/QOL was 40.3% (95% CI, 33.6%-46.9%) among evaluable patients with brain metastases (n = 146). The 12-month deterioration-free rates for cognitive, emotional, physical, role, and social functioning were 53.5%, 63.3%, 56.8%, 44.5%, and 54.3%, respectively.
Patients with stable brain metastases (n = 87) showed an estimated 12-month deterioration-free rate of 41.0% (95% CI, 32.3%-49.6%) in terms of GHS/QOL. Those with active brain metastases (n = 59) had a rate of 39.2% (95% CI, 28.9%-49.4%).
Neurological Stability
The study also assessed neurological function. "Estimated deterioration-free rates at 12 months were above 50% for cognitive, emotional, physical, and social functioning, as well as pain scores, regardless of the presence or absence of stable/active baseline brain metastases," noted Dr. Nadia Harbeck, director of the Breast Center at LMU University Hospital in Munich, Germany, and coauthors in a poster presentation of the data. The majority of patients had neurological stability at first score post baseline (86.6%), which was maintained throughout treatment in 55.1% of patients in the baseline brain metastases cohort and 72.9% of patients without baseline brain metastases.
Progression-Free Survival and Objective Response
Primary findings from DESTINY-Breast12 demonstrated that the 12-month PFS rates among all patients with brain metastases (n = 263), those with stable brain metastases (n = 157), and those with active brain metastases (n = 106), were 61.6% (95% CI, 54.9%-67.6%), 62.9% (95% CI, 54.0%-70.5%), and 59.6% (95% CI, 49.0%-68.7%), respectively. The median PFS in the overall population was 17.3 months (95% CI, 13.7-22.1). The respective confirmed ORRs were 51.7% (95% CI, 45.7%-57.8%), 49.7% (95% CI, 41.9%-57.5%), and 54.7% (95% CI, 45.2%-64.2%).
Implications for Treatment
These results suggest that Enhertu not only provides clinical benefit in terms of survival and response rates but also helps maintain the quality of life for patients with HER2-positive metastatic breast cancer, including those with brain metastases. This is particularly important as brain metastases can significantly impact a patient's neurological function and overall well-being.
Enhertu received accelerated approval from the FDA in December 2019 for patients with unresectable or metastatic HER2-positive breast cancer after two or more prior anti-HER2-based regimens. Full approval was granted in May 2022 based on the DESTINY-Breast03 trial.
