A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study Journal Article

   

Authors:	Coleman, R. L.; Sill, M. W.; Bell-Mcguinn, K.; Aghajanian, C.; Gray, H. J.; Tewari, K. S.; Rubin, S. C.; Rutherford, T. J.; Chan, J. K.; Chen, A.; Swisher, E. M.
Article Title:	A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study
Abstract:	Background Veliparib 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). Methods Eligibility 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). Results The 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. Conclusions The single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation. © 2015 Elsevier Inc. All rights reserved.
Keywords:	adult; cancer chemotherapy; cancer survival; clinical article; treatment outcome; treatment response; aged; middle aged; drug tolerability; neutropenia; cancer recurrence; drug dose reduction; drug efficacy; drug safety; drug withdrawal; monotherapy; skin manifestation; cancer patient; ovarian cancer; progression free survival; antineoplastic metal complex; multiple cycle treatment; peritoneum cancer; phase 2 clinical trial; sensory neuropathy; gastrointestinal symptom; kidney disease; leukopenia; thrombocytopenia; dehydration; peripheral neuropathy; genetic association; cancer resistance; alanine aminotransferase blood level; aspartate aminotransferase blood level; tumor suppressor gene; alanine aminotransferase; aspartate aminotransferase; multicenter study; ovary carcinoma; cancer fatigue; mental disease; open study; eye disease; uterine tube carcinoma; cancer control; connective tissue disease; toxicity; neurologic disease; metabolic disorder; thorax disease; musculoskeletal disease; vascular disease; breast disease; infectious complication; phase ii trial; lung complication; genital system disease; germline mutation; parp inhibitor; veliparib; urinary tract disease; cancer prognosis; mediastinum disease; chemotherapy induced nausea and vomiting; nutritional disorder; inner ear disease; chemotherapy induced anemia; human; female; priority journal; article; patient history of chemotherapy; brca1, brca2 mutation; infestation
Journal Title:	Gynecologic Oncology
Volume:	137
Issue:	3
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2015-06-01
Start Page:	386
End Page:	391
Language:	English
DOI:	10.1016/j.ygyno.2015.03.042
PROVIDER:	scopus
PMCID:	PMC4447525
PUBMED:	25818403
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84930047827&partnerID=40&md5=681d7010d11cdf10f00b90647b9804c6
Notes:	Export Date: 2 July 2015 -- Source: Scopus

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