Long-term responders to sacituzumab govitecan in metastatic triple-negative breast cancer: Real-world outcomes and predictors from a multicenter Italian cohort.

Abstract

1129 Background: Sacituzumab govitecan (SG) has reshaped the treatment landscape of metastatic triple-negative breast cancer (mTNBC), demonstrating superior survival outcomes compared with standard chemotherapy in the ASCENT trial. Despite the overall poor prognosis of mTNBC, a subset of patients experiences remarkably durable responses and prolonged survival, far exceeding the median progression-free survival (PFS) observed in pivotal trial. However, the clinical characteristics and prognostic determinants of these "long-term responders" (LTRs) remain poorly defined, and real-world evidence specifically addressing this population is currently lacking. This multicenter study aims to characterize outcomes and identify potential predictors of long-term benefit from SG in a real-world setting. Methods: This multicenter observational analysis included 271 patients with mTNBC treated with SG across 18 Italian cancer centers, within a study incorporating both retrospective and prospective cohorts (NCT02284581). LTRs were defined as patients achieving a real-world PFS (rwPFS) ≥ 9 months. The primary endpoint was rwPFS, while secondary endpoints included real-world overall survival (rwOS) and objective response rate (ORR). Survival outcomes were estimated using the Kaplan-Meier method, and independent prognostic factors were identified using Cox proportional hazards models. Results: Seventy-four of 271 patients (27.3%) were identified as LTRs. Within this cohort, median rwPFS was 14 months (95% CI: 13.3–16.3) and median rwOS was 25.6 months (95% CI: 21.0–NR). The ORR was 68.9% (all partial responses; n=51), while 29.7% of patients (n=22) achieved stable disease. On multivariable analysis, previous therapy with immune checkpoint inhibitors (ICI) was independently associated with a reduced risk of progression (HR 0.47; 95% CI: 0.22–0.98; p=0.04). De novo metastatic disease also showed a trend towards a lower risk of progression (HR 0.44; 95% CI: 0.16–1.17; p=0.10). Conversely, treatment with SG in the third line compared with the second line was associated with a higher risk of progression (HR 2.04; 95% CI: 1.02–4.07; p=0.04). No significant association were observed for brain metastases (p=0.37), BRCA mutation status (p=0.33), or visceral involvement (p=0.27). Conclusions: In real-world setting, more than 25% of mTNBC patients experience a durable benefit from SG. Prior exposure to immunotherapy and earlier use of SG in the second-line setting were associated with a higher likelihood of LTR, while de novo disease showed a favourable trend. Notably, the presence of brain or visceral metastases did not preclude prolonged benefit. These findings suggest that a subset of patients with mTNBC may derive sustained clinical benefit from SG and support its use earlier in the treatment sequence. Clinical trial information: NCT02284581 .