Background: Trastuzumab deruxtecan (T-DXd) has transformed the treatment landscape of human epidermal growth factor receptor 2-positive (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).
Objectives: To evaluate the real-world effectiveness and safety of T-DXd in patients with HER2+ mBC in Türkiye.
Design: A multicenter retrospective cohort study.
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 27 oncology centers in Türkiye. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (rwOS). Secondary endpoints included response rate, safety (with adverse events (AEs) graded according to CTCAE v5.0), and evaluation of the first post-T-DXd treatments.
Results: A total of 269 patients were included. The median age was 49 years (interquartile range: 42-59), and the median follow-up was 12.9 months. The median rwPFS was 17.9 months (95% confidence interval: 13.3-22.5), and the median rwOS was 35.7 months (95% confidence interval: 27.8-43.6). The objective response rate was 71.4%, and the disease control rate was 95.2%. Patients receiving T-DXd in the second line experienced significantly longer rwPFS compared with those treated in later lines (p < 0.001). Treatment-related AEs of any grade occurred in 68.4% of patients. Interstitial lung disease was reported in 21 patients (7.8%), with 4 cases being grade ⩾3.
Conclusion: In this large national 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.
Keywords: HER2+ metastatic breast cancer; efficacy; real-world evidence; safety; trastuzumab deruxtecan.
Real-world use of trastuzumab deruxtecan for HER2-positive metastatic breast cancer HER2-positive metastatic breast cancer is an aggressive form of breast cancer that often requires multiple lines of treatment. Trastuzumab deruxtecan is a targeted cancer medicine that combines an antibody with a chemotherapy drug, allowing treatment to be delivered directly to cancer cells. Clinical trials have shown that this treatment can be very effective, but patients enrolled in trials may not fully represent those treated in everyday clinical practice. In this study, we examined how trastuzumab deruxtecan performed in real-world settings across Turkiye. We collected and analyzed data from 269 patients treated at 27 cancer centers. This allowed us to understand how well the drug worked and how safe it was outside of clinical trials. We found that many patients experienced meaningful disease control, with most patients showing tumor shrinkage or stabilization. Patients who received trastuzumab deruxtecan earlier in their treatment course tended to benefit the most. Overall survival and the time patients lived without cancer progression were similar to, or better than, results previously reported in clinical trials. Side effects were generally manageable. A small number of patients developed lung inflammation, a known risk of this treatment, highlighting the importance of careful monitoring. In summary, our findings show that trastuzumab deruxtecan is an effective and reasonably safe treatment for HER2-positive metastatic breast cancer in routine clinical care. These results support its use beyond clinical trials and provide valuable evidence from a middle-income country setting, helping doctors and patients make informed treatment decisions.
© The Author(s), 2026.