Safety and efficacy of biosimilar TDM-1: A real world retrospective study.

3022 Background: Ado-Trastuzumab emtansine (TDM1), an antibody-drug conjugate demonstrated significant efficacy in both metastatic and adjuvant treatment of HER 2 Positive Breast cancer. Cost of the drug was prohibitive for use in Low and Middle income countries (LMIC). A biosimilar version of TDM1 was introduced in India at a lower price in May 2021. Since then, the use of TDM1 in deserving patients has increased. We aimed to study the safety and efficacy of biosimilar TDM1 in our center. Methods: We retrospectively analysed the case records of all patients who were prescribed biosimilar TDM1 at our institute from 01.06.2021 to 20.10.2023. Indication for TDM1, line of therapy in which used, number of cycles used, response rates, adverse events, progression free survival and overall survival were calculated using simple statistical methods. The usage of any TDM1 after May 2021 was compared to the previous years’ usage. Results: A total of 116 patients were prescribed biosimilar TDM1 in the study period. Out of them, 51 patients received the drug in the adjuvant setting and 65 for advanced stage disease. Early stage (n=51): Out of the 51 patients, 32 (62.7%) completed planned cycles, 14 (27.5%) ongoing; 3 (5.9%) discontinued due to social reasons, 2 (3.9%) changed treatment due to adverse events. All of them tolerated the therapy well. Common adverse effects were fatigue. Only 5 patients (21.7%) required romiplostim for therapy related thrombocytopenia. None of them had grade ≥3 adverse affects. Advanced stage (n=65): At a median follow up of 9 months, 30 patients (46.2%) progressed; 15 (23%) ongoing; 15 (23%) defaulted due to various social reasons; 5 (7.7%) discontinued due to intolerance. The median number of cycles received was 8 cycles (IQR 5-13). Majority of them received TDM1 in the second line (84.6%). Response evaluation was available for 52 patients who completed at least three cycles of TDM1. Objective response rate was noted in 33 patients (50.8%). Clinical benefit rate (CR+PR+SD) was seen in 39 patients (75%). 5 patients (9.6%) had a Complete response, 28 (53.8%) had Partial response and 6 (11.5%) had a stable disease. The median duration of response was 5 months. The median Progression Free survival was 8 months (5.7– 10.2m) and the projected overall survival was 18 months (16.1-19.9 m). No serious adverse event or cardiac compromise was encountered. 3 patients had thrombocytopenia. One patient succumbed to non-neutropenic Septic shock. In a retrospective data analysis, TDM1 was used in 17 patients in one calendar year prior to the availability of generic TDM1. In the subsequent year, 60 patients received TDM1 at least once in either indication. Conclusions: The availability of biosimilar TDM1 increased the reach to deserving patients. No new adverse events were identified. The safety and efficacy of the biosimilar TDM1 were comparable.