Final results of a phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.
547 Background: Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (BC) is currently associated with 3-4 years survival and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T forms cytotoxic complexes with XPG inducing apoptosis, thus, the inhibitory effects of T may depend on XPG presence. In fact, a better response to T in BC pts with XPG RNA overexpression has been observed. Methods: Pts withHR positive, HER2 negative advanced BC, pretreated with anthracyclines and/or taxanes, who had progressed after 2-5 chemotherapy lines, were stratified according to their XPG expression from paraffin embedded tumor samples, to stratum A (XPG high [>3]) or to stratum B (XPG low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial) and treated with T (1.3 mg/m2 in 3-hour iv infusion every 3 weeks). Primary endpoint: to evaluate the efficacy of T as progression free survival rate at 4 months (PFS4) according to XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety in XPG high and XPG low pts. Statistical methods: A 2-stage design was chosen: at a 1st stage, 20 pts were enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint was done once 40 evaluable pts were recruited. If ≥ 7 out of 20 pts achieved PFS4, recruitment would continue to a maximum of 50 pts per stratum. Results: 44 pts (21 XPG high and 23 XPG low) were enrolled from three countries and five centers. Efficacy is shown in the Table. Most frequent AEs were nausea (54%) and fatigue (70%). ALT increase G4 occurred in 7% of pts and neutropenia G4 in 28%. Conclusions: Trabectedin showed modest activity in advanced HR-positive, HER2-negative BC previously treated with anthracyclines and taxanes, with an acceptable safety profile. XPG does not seem to be a predictor of outcome to T treatment in this patient population. Clinical trial information: 2010-022968-13. [Table: see text]