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Sub-category:
Metastatic Breast Cancer
Category:
Breast Cancer--Metastatic Breast Cancer
Meeting:
2009 ASCO Annual Meeting
Abstract No:
3
Citation:
J Clin Oncol 27:18s, 2009 (suppl; abstr 3)
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
Abstract:
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 |
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Abstract Disclosures
Faculty and Discussant Disclosures
Annual Meeting Planning Committee Disclosures
2009 Annual Meeting Proceedings Part I Errata
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by J. O'Shaughnessy:
Presentations by J. O'Shaughnessy:
Educational Book Manuscripts by J. O'Shaughnessy:
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