Abstract
Highlights•
Veliparib demonstrated single agent activity among recurrent ovarian cancer patients carrying a germline BRCA1/2 mutation
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Adverse events were observed but generally mild and managed conservatively
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Clinical responses were observed among enrolled with platinum-sensitive and -resistant recurrent disease
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 400 mg orally BID with one cycle being 28 days. 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 57 years (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 8.18 months.
ConclusionsThe single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation.
Keywords veliparib;
ovarian cancer;
PARP inhibitor;
toxicity;
Phase II trial;
BRCA1, BRCA2 mutation