Final Results of a Randomized Phase II Study Demonstrating Efficacy and Safety of BSI-201, a Poly (ADP-Ribose) Polymerase (PARP) Inhibitor, in Combination with Gemcitabine/Carboplatin (G/C) in Metastatic Triple Negative Breast Cancer (TNBC).
O'Shaughnessy J, Osborne C, Pippen J, Patt D, Rocha C, Ossovskaya V, Sherman B, Bradley C Baylor Sammons Cancer Center, Dallas, TX; Texas Oncology, Dallas, TX; Texas Oncology Cancer Center, Austin, TX; US Oncology, Dallas, TX; BiPar Scienes, Inc., South San Francisco, CA
Background: TNBC is an aggressive breast cancer subtype which 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 G/C in subjects with metastatic TNBC. Methods: Eligible subjects had measurable disease and received ≤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; IV) and carboplatin (AUC = 2; IV) were given on days 1 and 8, and BSI-201 (5.6 mg/kg; IV) on days 1, 4, 8, and 11 every 21 days. Endpoints were clinical benefit rate (CBR = CR + PR + SD ≥6 months), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: Preliminary analyses of all 116 dosed patients showed that, based on all patient visits through March 2009, BSI-201 + G/C improved CBR, ORR, median PFS, and median OS, compared with G/C alone. The frequency and nature of adverse events did not differ between arms.
|(n=57)||(n=59)||(95% CI)||P value|
|Median PFS, months||3.3||6.9||0.34 (0.20-0.58)||<0.0001|
|Median OS, months||5.7||9.2||0.35 (0.19-0.65)||0.0005|