Real-world outcomes of breast cancer central nervous system metastases treated with sacituzumab govitecan.

Abstract

e13095 Background: Prior studies indicate that therapeutic concentrations of sacituzumab govitecan (SG) penetrate the central nervous system (CNS), but real-world data about its intracranial efficacy are limited. Methods: In this single-center retrospective study, we identified patients (pts) with metastatic breast cancer (MBC) with CNS metastases (including brain metastases (BM), leptomeningeal disease (LMD), or both) treated with SG from 2019-2025. Chart review identified treatment history and survival outcomes. CNS and extra-CNS response to SG was verified by independent neuro-radiologist imaging review using RECIST1.1 and Response Assessment in Neuro-Oncology criteria. Results: We identified 30 pts with MBC and CNS disease who received SG. All pts were female with median age 57 yrs (range 36-76). 16 pts (53.3%) had hormone receptor positive (HR+)/human epidermal factor-2 negative (HER2-) disease and 14 pts (46.7%) had triple negative breast cancer (TNBC). Median lines of prior chemo was 3 and 2 for HR+/HER2- and TNBC respectively. 27 pts (90.0%) received prior CNS-directed radiation (n = 17 stereotactic radiosurgery (SRS), n = 3 whole brain (WBRT) or craniospinal radiation, n = 7 SRS and WBRT). At time of SG start, 22 pts (73.3%) had BM, 3 (10.0%) had LMD, and 5 (16.7%) had BM and LMD. Of 27 pts with BM, 20 (74.1%) had stable BM (median time since radiation 1.2 months (mo)) and 7 (25.9%) had active BM. Of the 8 pts with LMD, 4 (50.0%) received prior LMD-directed radiation (median time since radiation 2.1 mo). The table shows CNS and extra-CNS objective response rate (ORR), clinical benefit rate (CBR) at 6 mo, median time to treatment failure (TTF), median CNS and extra-CNS progression-free survival (PFS), and median overall survival (OS). All CNS responses were partial responses and occurred in pts who had received CNS-directed radiation < 1 mo prior to SG start (4 BM, 2 BM/LMD). Conclusions: In a real-world population of pts with MBC and CNS disease, SG demonstrated a modest intracranial response, with a 20% CNS ORR (all objective responses in pts with prior radiation, none in pts with active BM/LMD). Median CNS PFS was 4.5 mo. Limitations of this retrospective data include variations in number of prior therapies, type/timing of prior radiation, and CNS imaging frequency. Larger prospective studies are needed to better characterize CNS response to SG and to identify predictors of CNS response. All pts HR+/HER2- TNBC CNS ORR, % (n) 20.0 (6/30) 25.0 (4/16) 14.3 (2/14) Extra-CNS ORR, % (n) 6.9 (2/29) 0.0 (0/16) 15.4 (2/13) CNS CBR at 6 mo, % (n) 26.7 (8/30) 18.8 (3/16) 35.7 (5/14) Extra-CNS CBR at 6 mo, % (n) 27.6 (8/29) 18.8 (3/16) 38.5 (5/13) Median TTF, mo (interquartile range (IQR)) 3.7 (2.0-6.7) 3.2 (2.0-6.2) 4.5 (1.6-9.4) Median CNS PFS, mo (IQR) 4.5 (2.3-8.5) 4.4 (0.8-4.9) 5.1 (2.3-8.5) Median Extra-CNS PFS, mo (IQR) 3.6 (1.9-9.0) 2.5 (1.6-5.7) 4.5 (2.1-9.3) Median OS, mo (IQR) 11.7 (6.2-24.0) 8.2 (5.9-24.0) 11.8 (6.7-39.1)