Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial.
Sub-category: Metastatic Breast Cancer
Category: Breast Cancer--Metastatic Breast Cancer
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:18s, 2009 (suppl; abstr 3)
Abstract No: 3
Session: Plenary Session including Science of Oncology Award and Lecture
Type: Plenary Presentation
Time: Sunday May 31, 1:00 PM to 4:00 PM
Location: Level 2, West Hall D2
Author(s): J. O'Shaughnessy, C. Osborne, J. Pippen, M. Yoffe, D. Patt, G. Monaghan, C. Rocha, V. Ossovskaya, B. Sherman, C. Bradley; Baylor Sammons, Texas Oncology, US Oncology, Dallas, TX; Cancer Centers of North Carolina/US Oncology, Raleigh, NC; Texas Oncology Cancer Center, US Oncology, Austin, TX; Kansas City Cancer Center, US Oncology, Kansas City, MO; BiPar Sciences, Inc., Brisbane, CA
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
The table didn't copy well. But compared to G/C base therapy, drug had Clinical Benefit Rate (CR + PR + SD =6 months) of 52% vs. 12%. PFS 211 days vs. 87 days. Med OS of >254 days vs. 169 days.
All the PARP inhibitors that I know of have been taken out by big pharm. Last I counted, there were like 6 in development.