Real-world Efficacy and Safety of Trastuzumab Deruxtecan in HER2-positive Metastatic Breast Cancer: A Multicenter Retrospective Study from Türkiye

Abstract

Objective: Trastuzumab deruxtecan (T-DXd) is a novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate that has demonstrated significant clinical activity in patients with HER2-positive metastatic breast cancer (mBC) in multiple pivotal trials. However, data regarding its effectiveness and safety in real-world settings, particularly from underrepresented regions such as Türkiye, remain limited. Material and Methods: This retrospective, multicenter observational study included HER2-positive mBC patients [immunohistochemistry (IHC) score of 3+, or IHC score of 2+ with in situ hybridization-positive gene amplification] who received T-DXd after at least one prior line of systemic therapy. Clinical outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), were evaluated. Subgroup and univariate Cox regression analyses were conducted to assess prognostic factors. Adverse events (AEs) were recorded and graded according to the Common Terminology Criteria for AEs version 5.0 (CTCAE v5.0). Results: A total of 39 patients were included. The ORR was 89.7% and the DCR was 100%. Median PFS and median OS were not reached at the time of analysis. In univariate analysis, a better Eastern Cooperative Oncology Group performance status and receipt of T-DXd in earlier treatment lines were associated with improved survival outcomes. AEs were generally manageable; grade ≥3 toxicity occurred in 15.4% of patients. Interstitial lung disease (ILD) was observed in 7.7% of patients, leading to treatment discontinuation in one patient. Conclusion: T-DXd demonstrated high clinical efficacy and manageable toxicity in a real-world cohort of Turkish patients with HER2-positive mBC. These results are consistent with those reported in clinical trials and support the use of T-DXd as an effective treatment option in routine clinical practice. Our findings also highlight the importance of early identification and management of treatment-related AEs, particularly ILD.