Abstract PS5-03-14: Clinical features and drug-drug interactions of patients treated with Sacituzumab Govitecan for metastatic triple-negative breast cancer: a multicenter correlative real-world updated analysis

Abstract Background: Sacituzumab Govitecan (SG), an antibody-drug conjugate (ADC) targeting TROP2, has demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) compared to standard chemotherapy in previously treated patients with metastatic triple-negative breast cancer (mTNBC). However, drug-drug interactions (DDIs), particularly in real-world settings, may influence the pharmacological activity of anticancer agents, potentially affecting both treatment efficacy and toxicity. Drug-PIN® (Personalized Interactions Network) is a tool designed to detect DDIs and integrate them with demographic, clinical, and biochemical patient data. In this multicenter retrospective analysis, we aim to evaluate the impact of clinical toxicites and DDIs on treatment outcomes in patients receving SG in a real world context. Methods: Toxicities, drug-drug interactions (DDIs), and clinical outcomes—including PFS and OS— in patients with mTNBC treated with SG in routine clinical practice were retrospectively collected from 11 Italian centers, as part of the NCT02284581 multicenter study. DDIs were assessed using the Drug-PIN® platform, which generated a Drug-PIN® score and assigned each patient to a Drug-PIN® tier: green (no clinically significant DDIs), and yellow to red (increasing DDI severity). Patients with relevant DDIs (tiers yellow to red) were compared to those without significant interactions (tier green). PFS and OS were estimated using the Kaplan-Meier method. The association between Drug-PIN® classification and clinical outcomes was assessed through multivariate logistic regression. Results: A total of 123 pts were included. Patient’s characteristics are reported in table 1. Median time from diagnosis of mBC to SG start was 17 months (range 0- 117). Among pts taking any medications, 20 pts (16.3%) had a relevant DDIs. Median rwPFS was 5.0 months in pts without any DDIs and 2.8 months in patients with DDIs [HR 1.89 (1.14-3.15) p 0.0138]. Using a multivariate model, both Drug-PIN tier [green vs other; HR 2.18 (1.3-3.5); p 0.0015] and presence of brain metastases at baseline [HR 1,62 (1,07-2,47) p 0,022] resulted as independent predictor of shorter PFS. Median OS was numerically higher but not statistically significant (p 0.098) in pts without DDIs [7.57 months vs 5.3 months [HR 1.69 (0.91-3.15)]. No significant association among DDIs and the report of common treatment related toxicity or dose reduction was detected. Conclusion: In our real-world cohort, a low rate of clinically relevant DDIs was observed. While DDIs were associated with shorter PFS, no differences in toxicity or dose modifications emerged. Further investigations are needed to assess the potential impact of DDIs in mBC pts treated with ADCs. Citation Format: R. Caputo, C. Martinelli, M. Piezzo, G. Buono, V. Di Lauro, R. Buonaiuto, A. Verrazzo, D. Cianniello, M. V. Bonomo, F. Pantano, S. Scagnoli, S. Cocco, G. R. Ricciardi, F. Giotta, L. S. Stucci, N. Staropoli, S. Turano, M. V. Sanò, P. Trasacco, L. Orlando, L. Del Mastro, A. Fabi, M. De Laurentiis, A. Botticelli. Clinical features and drug-drug interactions of patients treated with Sacituzumab Govitecan for metastatic triple-negative breast cancer: a multicenter correlative real-world updated analysis [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 PS5-03-14.