Abstract PS5-05-14: Real-world outcomes of trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer: Turkish oncology group multicenter study

Abstract Background: Trastuzumab deruxtecan (T-DXd) has transformed the treatment landscape of HER2+ metastatic breast cancer (mBC), with significant improvements in survival reported in clinical trials. However, limited data exist regarding its performance in real-world settings, particularly in lower-middle-income countries (LMICs). We aimed to evaluate the real-world effectiveness and safety of T-DXd in patients with HER2+ mBC in Türkiye. Methods: This multicenter, retrospective cohort study, conducted by the Turkish Oncology Group, evaluated the real-world outcomes and tolerability of T-DXd in patients with HER2+ mBC across 22 oncology centers in Türkiye. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and safety outcomes. Results: A total of 206 patients were included. The median age was 49 years (IQR: 42-59), and the median follow-up was 11.5 months. Among all patients, 72.3% had HER2 IHC 3+ disease, and 61.7% were HR-positive. T-DXd was administered in second line in 54 patients (26.2%), as third-line therapy in 63 patients (30.6%), and in the fourth line or beyond in 90 patients (43.7%). Patients had received a median of two lines of prior therapy (range: 0-8). The median rwPFS was 16.8 months (95%CI: 12.7-20.9), and the median OS was 29.2 months (95%CI: 22.1-36.3). Among the 192 patients evaluable for response, the ORR was 77.6% and the disease control rate (DCR) was 91.7%. Second line use of T-DXd in was associated with significantly longer rwPFS compared to later lines (p = 0.004). Treatment-related adverse events (AEs) of any grade occurred in 59% of patients. Interstitial lung disease (ILD) was reported in 20 patients (9.7%), with 4 cases being grade 3 or higher. Among the 12 patients with grade 1 ILD eligible for rechallenge, 83.3% (10/12 patients) were rechallenged. Conclusion: In this large real-world cohort from an LMIC, T-DXd demonstrated robust antitumor activity and a manageable safety profile in patients with HER2+ mBC. These findings are consistent with prior clinical trial data and support the applicability of T-DXd in broader clinical settings. Citation Format: T. Sahin, F. Kemik, H. Muglu, S. Biter, S. Tunbekici, A. Oruc, A. Guren, K. Kaban, M. Aykan, B. Koylu, O. Ekinci, I. Deliktas Onur, A. Kalem, O. Altunok, M. Seyyar, B. Guney, O. Akdogan, M. Yazici, N. Majidova, E. Esin, D. Cabuk, O. Yazici, R. Gursu, M. Yilmaz, H. Yesil Cinkir, O. Ates, E. Celik, N. Karadurmus, N. Mandel, I. Bayoglu, M. Araz, E. Goker, E. Bayram, D. Erdem, F. Selcukbiricik, G. Basaran, A. Sezer, A. Bilici, S. Gunduz, D. Guven, S. Aksoy. Real-world outcomes of trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer: Turkish oncology group multicenter study 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 PS5-05-14.