Abstract Background: The antibody-drug conjugate sacituzumab govitecan (SG) is approved for patients with metastatic triple-negative breast cancer (mTNBC) and hormone receptor (HR)+/Human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer (mBC). The impact of HER2-low status on treatment outcomes remains unclear. This study examines overall survival by subtype and prior therapies, explores HER2-low as a predictor of time to next treatment (TTNT), and evaluates TTNT as a potential surrogate for SG benefit. Methods: We identified 472 patients who received SG for HR+/HER2- mBC or mTNBC between 2020 and 2024. We compared overall survival (OS) by breast cancer subtype, treatment history, TTNT, and HER2-low status (1-2+ ISH neg) and investigated factors associated with OS. Results: The median age was 51 years (range, 24-85). Of the 472 patients, 292 (62%) had HER2-low status at any time and 184 (39%) had HER2-0 tumors. The median follow-up time was 9.1 months. Most (84%, n=396) received ≥1 prior therapy in the metastatic setting including chemotherapy (95%) while 34% (n=160) received ≥3 lines of therapy. Among HR+/HER2- mBC patients (n=118), 74% (n=87) received ≥3 lines of prior therapy. Among mTNBC patients (n=354), 38% (n=133) received prior ICI while 21% (n=73) received ≥3 lines of prior therapy. The median overall survival (mOS) duration was 15.3 months (95% CI: 13.5-17.5) for all patients, 12.1 months (95% CI: 8.6-14.9) for HR+/HER2- mBC patients, and 16.5 months (95% CI: 113.6-21.3) for mTNBC patients. Factors associated with worse OS were primary HR+ status (hazard ratio HR, 1.31; 95% CI, 1.00-1.71; p=0.052), anthracycline therapying metastatic setting (HR, 1.51; 95% CI, 1.05-2.18; p=0.027), and ≥3 prior lines of treatment (HR, 1.49; 95% CI, 1.13-1.96; p=0.004). There were no significant differences in survival based on race, age, or prior ICI therapy. Among 223 patients who were evaluable for TTNT, median TTNT was 5.9 months (range, 0.8-47.8 months), and 49.3% had a TTNT ≥6 months. Patients with a TTNT ≥6 months were more likely than those with a TTNT 6 months to have received ADCs as a subsequent line of treatment (30% vs 14%; p0.001). For the 223 patients evaluable for TTNT, the mOS was 16.4 months (95% CI, 13.7-20.3) for all patients, 19.9 months (95% CI, 10.2-not estimable) for HR+/HER2- mBC patients, and 16.4 months (95% CI, 13.6-20.3) for mTNBC patients, and HER2-low status at any time point was associated with better OS (HR, 0.68; 95% CI, 0.48-0.98; p=0.036). Conclusions: The survival outcomes in this real-world study were consistent with those reported for clinical trials. Among mTNBC patients, those who received fewer lines of prior chemotherapy had longer OS, and HER2-low status was significantly associated with OS. Prior ICI therapy did not significantly impact outcomes, but patients with 3 lines of prior therapy had worse outcomes, suggesting that earlier utilization of SG may be beneficial. Citation Format: A. Raghavendra, Z. Wang, R. Bssett Jr, S. Damodaran, C. Yam, V. Valero, P. Pohlmann, J. Litton, F. Meric-Bernstam, D. Tripathy, T. Adesoye. Real world outcomes of sacituzumab govitecan in hormone receptor-positive and triple-negative breast cancer: Impact of prior therapy 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 PS1-09-19.
Raghavendra et al. (Tue,) studied this question.