Abstract PS5-03-08: Effectiveness of sacituzumab govitecan in later-line treatment of mTNBC: real-world evidence from Poland, Czech Republic, and Slovakia according to prior first-line pembrolizumab use

Abstract Background Patients with metastatic triple-negative breast cancer (mTNBC) have limited treatment options and poor outcomes in later lines. Sacituzumab govitecan (SG) has shown benefit in this setting, including among those previously treated with programmed death-1 (PD-1) inhibitors. In the ASCENT trial, outcomes were numerically worse in patients with prior immunotherapy. As SG is used after progression on first-line chemoimmunotherapy with the PD-1 inhibitor pembrolizumab, concerns arise about its efficacy in this subgroup. Several biological and clinical mechanisms could support the hypothesis that prior anti-PD-1 therapy might influence SG efficacy, including selection of resistant clones, immune remodeling, functional decline, absence of mechanistic synergy, and acquired resistance to SN-38. This study evaluates SG outcomes according to prior use of pembrolizumab-based first-line treatment in Poland, the Czech Republic, and Slovakia. Materials and Methods We conducted a retrospective analysis of patients with mTNBC treated with SG across 18 oncology centers between August 2021 and May 2025. Patients were stratified by prior exposure to first-line palliative chemoimmunotherapy with pembrolizumab, as defined by KEYNOTE-355 criteria. Baseline data included prior treatment history, metastatic burden, and starting dose of SG. Outcomes assessed were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR), with tumor response evaluated per RECIST 1.1. Safety was analyzed based on adverse events (AEs) graded by CTCAE v5.0. Comparisons were performed using non-parametric and exact tests, and survival was analyzed using univariate Cox models with p<0.05 considered significant. Results Of the 302 evaluable women, 38 (12.6%) had previously received first-line anti-PD-1-based therapy. Baseline characteristics were similar between the groups. The median number of prior lines of palliative systemic therapy was 1 (IQR 1-2; range 1-7 in the anti-PD-1 group vs. 1-10 in the chemotherapy group; p=0.158). Brain metastases were present in 5/38 (13.2%) vs. 23/264 (8.7%) (p=0.372), and visceral metastases in 33/38 (86.8%) vs. 188/264 (71.2%) (p=0.066). A reduced starting dose of SG (≤8 mg/kg) was administered in 2/38 patients (5.3%) previously treated with first-line anti-PD-1 therapy and in 25/264 (9.5%) of others (p=0.550). Median OS was 10.74 months in the anti-PD-1 group and 11.43 months in the chemotherapy group (HR=1.30; 95% CI: 0.836-2.021; p=0.244). Median PFS was 3.22 vs. 4.44 respectively (HR=1.14; 95% CI: 0.782-1.662; p=0.497). ORR was 28.9% (11/38) in the anti-PD-1 group vs. 31.1% (82/264) in the chemotherapy group (p=0.939), while DCR was 60.5% (23/38) vs. 64.8% (171/264) (p=0.742). The median number of full SG cycles was 4 (IQR 2.25-9) in the anti-PD-1 group vs. 6 (IQR 3-11) (p=0.124). Toxicity profiles were similar. Grade ≥3 neutropenia occurred in 12/38 (31.6%) in the anti-PD-1 group and 124/264 (47.0%) in the chemotherapy group (p=0.137). Dose reductions due to AEs were required in 15/38 (39.5%) vs. 99/264 (37.5%) (p=0.956), and treatment delays occurred in 24/38 (63.2%) vs. 167/264 (63.3%) (p=1.000). Conclusions This real-world analysis provides insight into SG use after first-line pembrolizumab-based chemoimmunotherapy in mTNBC. While no clear reduction in efficacy or safety was observed, the impact of prior anti-PD-1 exposure remains clinically relevant. In light of the growing adoption of perioperative pembrolizumab and the anticipated shift of SG into earlier treatment lines, the impact of prior immunotherapy on SG performance should be further explored across diverse mTNBC settings and disease trajectories. Citation Format: J. Żubrowska, M. Kubeczko, M. Pieniążek, A. Polakiewicz-Gilowska, M. Malejčíková, A. Konieczna, M. Holánek, I. Kolářová, R. Soumarová, H. Študentová, A. Młodzińska, K. Winsko-Szczęsnowicz, M. Lisik-Habib, A. Pękala, D. Krejčí, J. Šustr, I. Danielewicz, M. Szymanik-Resko, T. Ciszewski, L. Rusinova,, A. Rudzińska, B. Czartoryska-Arłukowicz, A. Łacko, M. Jarząb, R. Pacholczak-Madej, Z. Bielčiková, M. Püsküllüoğlu. Effectiveness of sacituzumab govitecan in later-line treatment of mTNBC: real-world evidence from Poland, Czech Republic, and Slovakia according to prior first-line pembrolizumab use [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 PS5-03-08.