• Robert L Coleman, Michael W Sill, Katherine Bell-McGuinn, Carol Aghajanian, Heidi J Gray, Krishnansu S Tewari, Steven C Rubin, Thomas J Rutherford, John K Chan, Alice Chen, and Elizabeth M Swisher.
• Dept. of Gynecologic Oncology & Reproductive Medicine, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rcoleman@mdanderson.org.
• Gynecol. Oncol. 2015 Jun 1; 137 (3): 386-91.

BackgroundVeliparib is a potent small molecule inhibitor of PARP-1/2, which is cytotoxic in tumor cells with deficiencies in BRCA1 or BRCA2. We studied the clinical activity and toxicity of veliparib in ovarian cancer patients carrying a germline BRCA1 or BRCA2 mutation (gBRCA).MethodsEligibility included three or fewer prior chemotherapy regimens, measurable disease and no prior use of a PARP inhibitor. Veliparib was administered at 400mg orally BID with one cycle being 28days. The two-stage Simon design was capable of detecting a 25% response probability with 90% power while controlling alpha=10% (at a 10% assumed null response probability).ResultsThe median age of the 50 eligible patients was 57years (range 37-94) and 14, 18, and 18 patients had 1, 2, and 3 prior therapies respectively. Thirty patients (60%) were platinum-resistant. The median number of cycles administered was 6 (1-27). There was one grade 4 thrombocytopenia. Grade 3 adverse events were: fatigue (n=3), nausea (2), leukopenia (1), neutropenia (1), dehydration (1), and ALT (1). Grade 2 events >10% were: nausea (46%), fatigue (26%), vomiting (18%), and anemia (14%). The proportion responding was 26% (90% CI: 16%-38%, CR: 2, PR: 11); for platinum-resistant and platinum-sensitive patients the proportion responding was 20% and 35%, respectively. The most common reason for treatment discontinuation was progression (62%). Twenty-nine patients are alive; two with SD remain on veliparib. The median PFS is 8.18months.ConclusionsThe single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation.Copyright © 2015 Elsevier Inc. All rights reserved.

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