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3 Background: TNBC is an aggressive breast cancer subtype that shares molecular and pathologic features with BRCA1-related breast cancers. BRCA-deficient cells are sensitive to inhibition of PARP1, a critical enzyme of cell proliferation and DNA repair, and thus represent a rational target of PARP inhibitor-based cancer therapy. The objectives of this study were to evaluate BSI-201, a potent PARP1 inhibitor, in combination with gemcitabine/carboplatin (G/C) in subjects with metastatic TNBC. Methods: Eligible subjects had measurable disease and had ≤2 prior cytotoxic regimens for ER-, PR-, and HER2-negative metastatic breast cancer. Patients were randomized (1:1) to G/C alone or G/C + BSI-201. Gemcitabine (1000 mg/m2) and carboplatin (AUC=2) were given on days 1 and 8, and BSI-201 (5.6 mg/kg; iv; biweekly) on days 1, 4, 8, and 11 every 21 days. Endpoints were clinical benefit rate (CBR = CR + PR + SD ≥6 months), progression-free survival (PFS) and overall survival (OS). Results: Analyses of the first 86 of a planned 120 patients showed that BSI-201 + G/C had improved CBR, median PFS, and median OS, compared with G/C alone. The frequency and nature of adverse events (AEs) did not differ between arms. Conclusions: This preliminary analysis demonstrates that BSI-201 + G/C significantly improves CBR, PFS, and OS, compared with G/C alone. BSI-201 + G/C was well tolerated, with BSI-201 adding no significant toxicity to G/C. Updated CBR, PFS, and OS for all 120 patients and exploratory correlative analyses of PARP expression and clinical response will be presented. G/C (n = 44) G/C+BSI−201 (n = 42) Hazard ratio (95% CI) P value CBR, % 12 52 0.0012 Median PFS, days 87 211 0.30 (0.15–0.59) 0.0003 Median OS, days 169 >254 0.24 (0.09–0.61) 0.0012 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BiPar Sciences, Inc.
O’Shaughnessy et al. (Sat,) studied this question.