NVTG-04 REAL-WORLD OUTCOMES WITH SACITUZUMAB GOVITECAN AMONG BREAST CANCER PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) METASTASES

Abstract Sacituzumab-govitecan (SG) demonstrated significant survival benefits over standard chemotherapy in pretreated triple-negative (TNBC) and hormone receptor-positive (HR+/HER2-) metastatic breast cancer (MBC) patients. Limited data on intracranial outcomes in MBC patients exist. We describe the real-world (RW) of intracranial efficacy and outcomes for SG in MBC patients with central nervous system metastases (CNS-mets). METHOD We retrospectively studied MBC patients with CNS-mets who began SG between 2018 and 2022, using an institutional MBC database. CNS involvement was subcategorized as active CNS-mets (new or progressive not yet treated with CNS-directed therapy) and leptomeningeal disease (LMD). An independent radiologist confirmed CNS response rates (rwCNS-RR) using RANO criteria. The Kaplan-Meier method estimated RW-CNS, bi-compartmental progression-free, and overall survival (rwCNS-PFS, rwBi-PFS, and OS). RESULTS 33 women were included: 10 HR+/HER2- and 23 TNBC. 13/33 (39%) had active CNS-mets and 8/33 (24%) had LMD (2 HR+/HER2- and 6 TNBC). the median time from MBC diagnosis to SG initiation was 1.79 years (q1q3, 1.02-3.79), a median of 3 (q1q3, 2-6) prior lines received for MBC and 28/33 (84.8%) received prior brain radiotherapy. rwCNS-RR was 4/30 (13%; 1/9 HR+/HER2-; 3/21 TNBC). After a median follow-up of 20.70wks (95%CI 3.28-127.41) from SG initiation, median rwCNS-PFS, rwBi-PFS, and OS were 12.7 wks (95%CI 8.6–18.6), 11.3 wks (95%CI 8.3–17.6) and 29.1 wks (95%CI 13.6-43.3), respectively. Among patients with active CNS-mets, rwCNS-RR was 1/13 (8%). Among patients with LMD, rwCNS-RR was 1/7 (14.3%), and median OS was 15.8 wks (IC95% 7.4-47.6). The site of progression on SG was 1/33 (3%) CNS-only, 10/33 (30%) non-CNS only, 17/33 (52%) both, and 5/33 (15%) unknown because deceased. CONCLUSION In this RW analysis, SG was associated with modest clinical activity and intracranial response rates in heavily pretreated MBC patients with CNS metastases. Effective treatments demonstrated in prospective studies are needed for this patient.