Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer

摘要: CRA501 Background: Olaparib (AZD2281; KU-0059436) is a novel, orally active PARP inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. A phase I trial identified 400 mg bd as the maximum tolerated dose (MTD) with an initial signal of efficacy ovarian cancers (ASCO 2008; abst 5510). The primary aim this study was to test olaparib confirmed BRCA1/BRCA2 carriers advanced refractory breast cancer. secondary assess safety and tolerability population. Methods: In international, multicenter, proof-of-concept, single-arm, II study, two sequential patient (pt) cohorts received continuous oral 28-day cycles initially at MTD, (27 pts), subsequently 100 bd, previously inhibitory pts). Eligibility criteria included mutation recurrent, measurable chemotherapy-refractory endpoint best objectiv...