Outcome of BRCA 1/2-Mutated (BRCA+) and triple-negative, BRCA wild type (BRCA-wt) breast cancer patients in a phase I study of single-agent veliparib (V).

Systemic Therapy
Session Type and Session Title: 
Oral Abstract Session B: Risk Assessment, Prevention, Early Detection, Screening, and Systemic Therapy
General Poster Session B: Risk Assessment, Prevention, Early Detection,  Screening, and Systemic Therapy
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 26; abstr 135)
Shalu Pahuja, Jan Hendrik Beumer, Leonard Joseph Appleman, Hussein Abdul-Hassan Tawbi, Ronald G. Stoller, James J. Lee, Yan Lin, Brian Kiesel, Jing Yu, Antoinette R. Tan, Chandra Prakash Belani, Helen K. Chew, Agustin A. Garcia, Robert Morgan, Alice P. Chen, Vincent L. Giranda, Stacie Peacock Shepherd, Edward Chu, Shannon Puhalla; University of Pittsburgh Cancer Institute, Pittsburgh, PA; University of Pittsburgh Medical Center, Pittsburgh, PA; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA; University of Pittsburgh, Magee-Womens Hospital of UPMC, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel Project and Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Penn State Hershey Cancer Institute, Hershey, PA; University of California, Davis, Sacramento, CA; University of Southern California, Los Angeles, CA; City of Hope, Duarte, CA; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Abbott Laboratories, Abbott Park, IL; University of Pittsburgh Medical Center, Women's Cancer Program at Magee-Womens Hospital of UPMC, Pittsburgh, PA

Abstract Disclosures


Background: Veliparib (V) (ABT-888) is an oral, potent inhibitor of PARP 1/2. PARP inhibitors have preclinical and clinical efficacy in BRCA+ malignancies. There are genotypic and phenotypic similarities between BRCA+ cancers, serous ovarian cancer and basal-like breast cancer and we postulated that these tumors types may be similarly sensitive to single-agent PARP inhibition. This study sought to establish the maximum tolerated dose (MTD), dose -limiting toxicities (DLT), pharmacokinetic and pharmocodynamic properties, and preliminary efficacy of chronically-dosed V in 2 cohorts of patients, BRCA+ and BRCA-wt (consisting of serous ovarian cancer and triple-negative breast cancer (TNBC). Methods: A 3+3 dose escalation phase I trial was performed. Nine dose levels (DL) were planned, and dose escalation started at 50 mg BID to a maximum of 500 mg BID to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). V was administered orally continuously on a 28 day cycle. BRCA+ and BRCA-wt patients were enrolled in 2 separate cohorts with 2 separate escalations. Results: 98 (70 BRCA+ and 28 BRCA-wt) pts have been enrolled. The maximum administered dose (MAD) was 500mg BID and the MTD/RP2D is 400mg BID for both cohorts. 59 BRCA+ pts and 24 BRCA-wt pts (21 TNBC and 3 ovary) were evaluable for response. ORR was defined as CR+PR and clinical benefit rate (CBR) as CR+PR+SD > 6 months. Results are summarized in the table. Conclusions: There is evidence of anti-tumor activity with V comparable to that of other PARP inhibitors in the BRCA+ population. There was indication of dose responsiveness with greater activity in this population at higher doses. There is less activity in the mostly TNBC, BRCA-wt population, although there was evidence of benefit in a small number of patients. Ongoing tissue correlative studies will help to identify potential mechanisms of sensitivity and resistance. Clinical trial information: NCT00892736.

All tumor types: BRCA+ 14/59 = 24% 13/35 = 37% 33/59 = 56% 22/35 = 63%
BRCA+ breast cancer 4/14 = 29% 3/5 = 60% 8/14 = 57% 4/5 = 80%
All tumor types: BRCA-wt 1/24 = 4% 0/5 = 0% 4/24 = 17% 0/5 = 0%
BRCA-wt breast cancer 1/21 = 5% 0/4 = 0% 4/21 = 19% 0/4 = 0%