TROP2 overexpression as predictor of outcome in patients with early triple-negative breast cancer. Exploratory analysis from the GEICAM_CIBOMA trial.

582 Background: Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic strategy for triple-negative breast cancer (TNBC), a subtype with limited treatment options and poor prognosis. Understanding the biological and prognostic/predictive implications of biomarkers for these ADCs could help refine appropriate adjuvant treatment for high-risk TNBC. TROP2-targeted ADC sacituzumab govitecan has demonstrated significant improvements in progression-free and overall survival in clinical trials involving the advanced TNBC setting. We sought to explore the prognostic/predictive value of TROP2 expression by immunohistochemistry (IHC) in early TNBC patients (pts) from the GEICAM_CIBOMA trial (NCT00130533). Methods: We evaluated TROP2 expression by IHC using an anti-TROP2 monoclonal antibody (clone ERP20043, Abcam) in tumors from a subset of 70 TNBC pts included in the trial. These patients received either 6 months therapy with capecitabine (n=35) or observation (n=35) after receiving standard (neo)adjuvant chemotherapy (trial recruitment between 2006 and 2011). Semi-quantitative Histoscore (H-score) was estimated to consider the following TROP2 expression categories: H-score 0 to <100: TROP2 low; H-score 100-200: TROP2 medium; H-score ≥200: TROP2 high. Median TROP2 H-score was also explored for pts categorization. Cox regression models were assessed to predict DRFS (primary endpoint), DFS and OS (secondary endpoints). Multivariate models were adjusted for confounding factors, including histological grade, stage, chemotherapy regimen, and treatment. Results: The TROP2 H-score median value was 165. Medium/high TROP2 expression (H-score ≥100) was observed in 27 (77%) pts treated with capecitabine, and 25 (71%) in the observation group. Higher TROP2 expression was associated with higher histological grade (p=0.032). Medium/high TROP2 expression significantly associated with better DRFS (univariate analysis, HR=0.41; 95%CI 0.19-0.90; p=0.026; multivariate analysis, HR=0.24; 95%CI 0.10-0.60; p=0.002). This prognostic value was confirmed at DFS (multivariate analysis, HR=0.33; 95%CI 0.14-0.77; p=0.010) and OS (multivariate analysis, HR=0.29; 95%CI 0.11-0.76; p=0.011). High TROP2 expression by median value (H-score ≥165) was also associated with better clinical outcome (DRFS univariate analysis, HR=0.43; 95%CI 0.19-0.97; p=0.041; multivariate analysis, HR=0.44; 95%CI 0.19-1.02; p=0.057). TROP2 expression categorization did not demonstrate predictive value of capecitabine benefit (DRFS interaction with treatment, p=0.852). Conclusions: In this GEICAM_CIBOMA trial sub-study, TROP2 overexpression by IHC was observed in 74% of the analyzed cases and significantly associated with better clinical outcome in early TNBC pts, in terms of DRFS, DFS, and OS. Clinical trial information: NCT00130533 .