Real-world clinical outcome of sacituzumab govitecan (SG) in HER2-negative metastatic breast cancer.

Abstract

e13047 Background: Sacituzumab govitecan (SG) is an anti-TROP2 antibody-drug conjugate (ADC) approved for the treatment of patients (pts) with HER2-negative (HER2-) metastatic breast cancer (MBC). While clinical trials have demonstrated the efficacy of SG, real-world data on its use and outcomes remain limited. Methods: This retrospective study was conducted in pts with HER2- MBC treated with SG at Cedars-Sinai Medical Center from 2018 to 2025. Clinicopathological features, treatment variables, and clinical outcome data were collected. Progress-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. “Cross-resistance” was defined as progressive disease (PD) observed at the first restaging scan on a second ADC after SG. Next generation sequencing (NGS) data were available in a subset of pts either before or after SG treatment. A multivariate Cox proportional analysis was performed to assess the association of pt and treatment characteristics and genomic alterations with PFS and OS in pts treated with SG. Results: A total of 91 pts (HR+HER2-, n = 38; TNBC, n = 53) were included. The median age was 58, with 58.2% White, 16.5% Black, and 15.4% Asian. Visceral metastatic disease was present in 66 pts (72.5%), and brain metastasis was present in 24 pts (26.4%). The median prior lines of chemotherapy was 2 (1-5) for HR+HER2- and 1 (0-5) for TNBC cohort. 28 pts (30.8%) received another ADC prior to SG, and 93% were trastuzumab deruxtecan (T-DXd). Among the 53 pts (58.2%) received post-SG treatment, the most common immediate therapies were eribulin (n = 14, 26.4%), T-DXd (n = 9, 17%), and gemcitabine/carboplatin (n = 7, 13.2%). Of the pts received T-DXd immediately after SG, cross-resistance was present in 4/9 pts, absent in 3/9 pts, with 2/9 pending. No significant difference in PFS of SG was observed between HR+HER2- and TNBC (median PFS 3.4 mo vs. 4.2 mo) (p = 0.93). SG showed improved PFS benefit as the 1st ADC vs. 2nd ADC in HR+ HER2- cohort with median PFS 7.7 mo vs 2.1mo (p = 0.0052) but not in TNBC cohort (median PFS 4.4 vs 3.5 mo, p = 0.87). NGS data in 54 pts (59.3%) showed the most common mutations were: TP53 (70.4%), PIK3CA (33.3%), PTEN (16.7%). Multivariate Cox proportional analysis assessing the impact of age, BC subtype, brain and visceral metastasis, ADC order, genomic mutation, and TMB on the PFS and OS of SG, revealed that SG used as the 1st ADC and the presence of TP53 mutation were associated with a trend toward improved PFS [HR 0.42 (0.17-1.0), p = 0.057] and [HR 0.46 (0.19-1.1), p = 0.074], respectively. Conclusions: This real-world study evaluated clinical and genomic factors associated with the outcome of SG treatment. SG demonstrated better PFS when used earlier in the treatment sequence, particularly in HR+HER2- cohort. Genomic profiling revealed TP53 mutations trended toward improved PFS. Further validations of these findings are needed to explore their implications for optimizing SG use.