Efficacy and safety of trastuzumab deruxtecan in HER2+ and HER2-low metastatic breast cancer: Real-world data from India.

e13023 Background: Trastuzumab deruxtecan (T-DXd) is a transformative therapy for HER2+ and HER2-low metastatic breast cancer (MBC). However, real-world data on Indian patients remains limited. Methods: : We conducted an ambispective review of the medical records of HER2+ and HER2-low MBC patients treated with T-DXd at All India Institute of Medical Sciences, New Delhi, India, between March 2021 and September 2024. Patients who received ≥1 dose of T-DXd following at least 3 lines of prior treatment, were included in the analysis. Primary prophylaxis with GCSF and appropriate antiemetics were used in all patients. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), overall response rate (ORR), and safety profile. Results: A total of 36 patients were included. Median age was 50 years (range: 30-67). Eighteen (n=18, 50%) patients were hormone receptor (HR) positive. The distribution of Eastern Cooperative Oncology Group (ECOG) performance status (PS) was as follows: 14 patients (38.9%) with PS 1, 18 patients (50%) with PS 2, and 4 patients (11.1%) with PS 3. T-DXd was administered as a 3rd line therapy in 15 patients (41.6%) and as a 4th line therapy in 21 patients (58.3%). All patients had visceral metastasis (8 patients had brain metastasis and 2 patients had leptomeningeal disease)along with bone metastasis in 8 patients . The median number of cycles administered was 6 (range: 2-18). Among the cohort, 7 patients (19.4%) had HER2-low status. With a median follow-up of 12 months, the median PFS was 9 months, and the median OS was 15 months. The ORR was 70% ( partial response 47.2%, stable disease 19.4% and complete response in 5.5%). Any-grade adverse events (AEs) occurred in 29 patients (80.5%), with the most common being nausea, anemia, and asthenia. Any grade Interstitial lung disease (ILD) was reported in 15patients (41.6%). One patient died due to ILD after the 6th cycle. Seven patients (19.4%) required hospitalization due to serious AEs (SAEs) mainly due to ILD. Treatment-emergent dose reductions or discontinuations occurred in 14 patients and 5 patients respectively . Conclusions: Our study supports the efficacy and safety of T-DXd in India in a real-world clinical setting with results being consistent across published literature. The high ILD rate may reflect the cohort's heavy prior treatment and relatively poor general condition. T-DXd can be introduced in the earlier line in the management of MBC to prevent toxicities and a better response rate. Early detection by thorough clinical examination, prompt chest-HRCT scans, and serum biomarker [ Krebs von den lungen-6 (KL-6), surfactant protein-D (SP-D)] monitoring, along with prompt intervention, may reduce ILD risk and improve outcomes.