Effectiveness and safety of sacituzumab govitecan in heavily pretreated metastatic HER2-negative breast cancer: A real-world multicenter analysis in China.

Abstract

e13104 Background: Sacituzumab govitecan (SG) is the first antibody-drug conjugate targeting trophoblast cell - surface antigen 2 (Trop-2). Clinical trials such as ASCENT and TROPiCS-02 have demonstrated that SG improves progression-free survival (PFS) and overall survival (OS) in metastatic triple-negative breast cancer (mTNBC) and HR+/HER2- breast cancer following prior therapy. While SG has been approved in China for two years, real-world data on its efficacy and safety in Chinese metastatic breast cancer (MBC) patients remain limited. This multicenter real-world study aimed to evaluate SG’s efficacy and safety in Chinese patients with HER2-negative MBC. Methods: Data were retrospectively collected from HER2-negative MBC patients treated with SG and received first radiological evaluation between June 2023 and October 2024. Outcomes included real-world progression-free survival (rwPFS), objective response rate (ORR), disease control rate (DCR), real-world overall survival (rwOS), and safety. Results: Fifty-eight patients were included, with a median age of 53.4 years. Patients had a median of three prior systemic treatments (range 1–10) for metastatic disease. The cohort included 43 TNBC patients (74.1%) and 15 HR+/HER2- patients (25.9%), with metastatic sites in the liver (55.2%), lung (41.4%), brain (22.4%), and bone (53.3%). The overall cohort showed an ORR of 36.2%, a DCR of 81.0%, and a median rwPFS of 3.9 months. For mTNBC, the ORR was 34.8%, DCR 79.1%, and median rwPFS 4.2 months. Among four mTNBC patients receiving SG combined with PD-1 inhibitors, the ORR reached 50.0%. In HR+/HER2- patients with median 2 lines of prior endocrine therapy, the ORR was 40.0%, DCR 86.7%, and median rwPFS 3.5 months. In 13 patients with brain metastases, the ORR was 30.7%, with a median rwPFS of 6.3 months. OS data remain immature; the 6-month OS rate was 76.8%. Safety analysis identified neutropenia (53.5%) and diarrhea (22.4%) as the most common adverse events (AEs), with grade ≥3 rates of 17.2% and 6.9%, respectively. Febrile neutropenia occurred in 3.5% of patients, while no ocular toxicity was observed. Granulocyte colony-stimulating factor (G-CSF) was used prophylactically in 34.5% of cases. Conclusions: This real-world study confirms the efficacy and manageable safety profile of SG in heavily pretreated Chinese patients with HER2-negative metastatic breast cancer. SG demonstrated significant disease control in both TNBC and HR+/HER2- subgroups, with consistent PFS. The observed efficacy in patients with brain metastases warrants further investigation. Lower rates of neutropenia and diarrhea compared to global trials may reflect enhanced supportive care, such as prophylactic G-CSF use. These findings provide valuable insights into the role of SG in Chinese clinical practice and highlight areas for future research to optimize outcomes.