Abstract PS5-08-14: Destiny-breast respond her2-low europe: description of first enrolled patients in the non-interventional study of t-dxd in her2-low metastatic breast cancer

Abstract DESTINY-Breast04 showed significantly longer PFS and OS in patients (pts) with HER2-low (IHC 1+ or IHC 2+/ISH-) mBC treated with trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy.1 As such, there was a shift from the binary HER2 classification towards a HER2 spectrum, including HER2-low as a targetable biomarker for T-DXd. The ongoing DESTINY-Breast Respond HER2-low Europe study (NCT05945732) aims to evaluate real-world effectiveness and safety of T-DXd in pts with HER2-low mBC. We report an initial snapshot of baseline characteristics and prior treatment lines. The design has been published.2 The study is enrolling pts with HER2-low mBC who received ≥1 prior line of chemotherapy in the metastatic setting and are being treated with T-DXd or standard chemotherapy, aiming to enroll 1010 pts from 206 sites across 10 European countries. Primary objective is effectiveness of T-DXd based on real-world time to next treatment, secondary endpoints include baseline demographics, clinical characteristics and other outcome parameters. The first pt was enrolled in Jan 2024. Data cutoff for initial baseline characteristics assessment was 15 April 2025. A total of 234 pts have been enrolled from 8 countries (Austria, Belgium, Denmark, France, Italy, Spain, Sweden and Switzerland). Most pts were female (98.3%). Median age was 62 yrs, 15% aged 75 yrs. Nearly half of pts had an ECOG score ≥1, 8.5% presenting with brain metastasis and 2.1% with lung-related comorbidities. HER2-low pts with HR+ (78.2%) and HR- (18.8%) disease were enrolled and HER2 status was categorized using the most recent biopsy (mostly using newly obtained tissue 61.5% vs archival tissue 36.3% from metastases 62.4% vs primary tumour 35.0%). Pts previously received a median of 3 prior lines in the metastatic setting. The most common treatments received were CDK4/6 inhibitor-based regimens (52.0%) in the first line, and chemotherapy in the second and third line (47.5% and 56.0%). The most common prior chemotherapy received for mBC was capecitabine (35.6%). An updated analysis will be available for presentation at SABCS, and results are expected to be consistent with the snapshot analysis. This initial snapshot analysis indicates that HER2-low mBC pts treated with T-DXd in the real-world are more diverse versus those in DESTINY-Breast04; the number of prior treatment lines is comparable while age and overall health status differ, highlighting the importance of ongoing recruitment to this large, longitudinal, observational study. Overall, initial data indicate that the DESTINY-Breast Respond HER2-low Europe study will add valuable insights on real-world effectiveness, treatment management, safety and quality of life for HER2-low mBC pts treated with T-DXd in the European region. 1. Modi, et al. NEJM. 2022;3887:9-20. 2.Guarneri, et al. Future Oncol. 2024;20:1237-50. Citation Format: V. Guarneri, J. Passos Coelho, F. P. Duhoux, D. Egle, J. García-Sáenz, F. Penault-Llorca, H. Wildiers, K. Zaman, P. Laeis, M. Lucerna, J. Pierga. Destiny-breast respond her2-low europe: description of first enrolled patients in the non-interventional study of t-dxd in her2-low metastatic breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-14.