Abstract PS2-04-09: Impact of prior treatment exposure and clinical-pathological factors on response and survival with Sacituzumab govitecan in advanced breast cancer: a consecutive real-world series

Abstract Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) approved for the treatment of advanced triple negative (TNBC) and estrogen receptor positive-HER2 negative (ER+/HER2-) breast cancer (BC). Real-world data on response determinants are limited. We evaluated clinical-pathological factors associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in a consecutive patient series treated in routine practice. Methods: This retrospective study included 74 consecutive female patients treated with SG at the Hospital Clinic of Barcelona between April 2022-April 2025. Clinical-pathological variables included tumor subtype, ECOG status, number of metastatic sites, visceral metastases, prior therapies, and Ki-67 index (pre-treatment or most recent metastatic biopsy). No patients had received prior ADC containing a TOP1 inhibitor payload. ORR was assessed radiologically according to RECIST version 1.1. ORR associations were tested by univariate logistic regression; survival by Kaplan-Meier and Cox models. Results: Median age was 57 years; 41 patients (54.9%) had TNBC and 33 (45.1%) ER+/HER2- BC. 61 patients had visceral disease (86%), 10 patients had brain metastasis (14%), 42 were ECOG status1 (59.2%), and 43 had 3 metastatic sites (60.6%). The median number of previous chemotherapy lines in metastatic setting was 2. The ORR was 34.3% (2.9% complete and 31.4% partial). Stable disease and progressive disease occurred in 22.9% and 42.8%, respectively. ORR was 44.4% among the 31 patients who had received fewer than three prior lines of chemotherapy, compared to 27.9% in the 43 patients treated in the third-line setting or beyond. In univariate logistic regression, having received ≥3 chemotherapy lines, compared to 3, was associated with significantly lower odds of response (odds ratio OR=0.07, 95% CI: 0.00–0.47, p=0.020). No statistically significant associations in ORR were observed for Ki-67 index (p=0.470). The median follow-up for overall population was 12 months (95% CI: 9-14): 8 months for ER+/HER2- (95% CI: 6-13), and 16 months for TNBC (95% CI: 14-NA). Median PFS was 4 months (95% CI: 3-6) in the overall population, 6 months (95% CI: 3-8) in ER+/HER2-, and 4 months (95% CI 2-5) in TNBC. Median OS, calculated from the start of SG, was 18 months (95% CI 9-20): 19 months in ER+/HER2- (95% CI NA-NA), and 8 months in TNBC (95% CI 5-18). In the Cox univariate regression, worse ECOG status (hazard ratio HR=2.58, p=0.002), ≥3rd-line setting (HR=4.01, p=0.001), and 3 metastatic sites (HR=1.77, p=0.048) were independently associated with shorter PFS. No statistically significant associations were observed between PFS and Ki-67 (p=0.650). TNBC subtype (HR=4.46, p=0.006), visceral disease (HR=7.85, p=0.046), and ECOG status 1 (HR=10.17, p0.001) predicted for shorter OS. In contrast, ER+/HER2- (HR=0.24, p=0.010) and prior endocrine therapy (HR=0.32, p=0.004) were associated with longer OS. No statistically significant associations were observed between OS and Ki-67 index (p=0.153). Conclusions: In this real-world cohort, SG demonstrated limited antitumor activity across both TNBC and ER+/HER2- breast cancer. Clinical benefits were greater in patients with limited prior treatment exposure, preserved ECOG status, and lower disease burden. These findings support the earlier use of SG. Citation Format: C. Gullotta, S. Cobo, B. Walbaum, M. Bergamino, R. Gómez-Bravo, O. Martínez-Sáez, F. Schettini, E. Segui, I. García-Fructuoso, T. Pascual, N. Chic, M. González-Rodríguez, G. Riu, E. Carcelero, A. Rodríguez-Hernández, E. Sanfeliu, P. Galván, M. Muñoz, M. Vidal, A. Prat, F. Braso-Maristany, B. Adamo. Impact of prior treatment exposure and clinical-pathological factors on response and survival with Sacituzumab govitecan in advanced breast cancer: a consecutive real-world series abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-09.