[3122] 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.

 G/CG/C+BSI-201Hazard Ratio 
 (n=57)(n=59)(95% CI)P value
CBR, %2162 0.0002
ORR, %1648 0.002
Median PFS, months3.36.90.34 (0.20-0.58)<0.0001
Median OS, months5.79.20.35 (0.19-0.65)0.0005

Conclusions: This analysis demonstrates that BSI-201 + G/C improved patient's outcomes, as measured by CBR, ORR, PFS and OS, compared with G/C alone. BSI-201 + gemcitabine/carboplatin was well tolerated and did not potentiate chemotherapy-related toxicities. Final data on CBR and ORR, as well as updated analyses of PFS and OS for all 116 dosed patients will be presented based on all patient visits through September 2009. Exploratory correlative analyses of PARP expression and overall clinical response will also be presented, as well as initial correlative analyses between number of metastatic therapies and clinical response.

Friday, December 11, 2009 5:30 PM

Poster Session 3: Tumor Biology: Novel/Emerging Therapeutic Targets (5:30 PM-7:30 PM)

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