Meeting
2013 ASCO Annual Meeting
Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCA-associated breast cancer.
Authors
George Somlo
City of Hope Cancer Center, Duarte, CA
George Somlo , Paul Henry Frankel , Thehang H. Luu , Cynthia Ma , Banu Arun , Agustin Garcia , Tessa Cigler , Gini F. Fleming , Harold A. Harvey , Joseph A. Sparano , Rita Nanda , Helen K. Chew , Timothy Jerome Moynihan , Linda T. Vahdat , Matthew P. Goetz , Arti Hurria , Joanne E. Mortimer , David R. Gandara , Alice P. Chen , Jeffrey N. Weitzel
Organizations
City of Hope Cancer Center, Duarte, CA, City of Hope Beckman Research Institute, Duarte, CA, City of Hope, Duarte, CA, Washington University School of Medicine in St. Louis, St. Louis, MO, The University of Texas MD Anderson Cancer Center, Houston, TX, University of Southern California, Los Angeles, CA, Weill Cornell Medical College, New York, NY, Alliance for Clinical Trials in Oncology, Chicago, IL, Milton S. Hershey Medical Center, Hershey, PA, Montefiore Medical Center, Bronx, NY, University of Chicago, Chicago, IL, University of California, Davis Cancer Center, Sacramento, CA, Mayo Clinic, Rochester, MN, University of California, Davis Comprehensive Cancer Center, Sacramento, CA, National Cancer Institute, Bethesda, MD
Research Funding
No funding sources reported
Background: The combination of platinum agents and PARP inhibitors may benefit patients (pts) with BRCA-associated metastatic breast cancer (MBC). We report on the response and clinical benefit rates when combining the PARP inhibitor veliparib (V) and carboplatin (carb) in a phase I trial. Methods: BRCA carriers with MBC were eligible. Carb starting at an AUC of 6 was given IV in 21-day cycles (C) and V was given orally twice daily (BID) at dose levels (L) L1 through L5. Results: Twenty-eight pts (26 eligible) carrying BRCA1 (12) or BRCA2 (15), or both (1) mutations were accrued between June 2010 and June 2012. The median age (32-66) was 45 years. The number (#) of prior chemotherapy regimens given for MBC was 1 (0-5); 70% of BCs were ER+, and 7% were HER2+. The schema, dose limiting toxicities (DLT) during C 1, median # of Cs on trial, and maximum tolerated dose (MTD) are shown. There were 3 (12%) complete and 9 (35%) partial responses (PR). Unconfirmed PR or stable MBC (median duration: 8 months [6-10+]) were seen in 7 pts (27%); the clinical benefit rate was74%. The median progression-free survival (PFS) is 7.8 months (95% CI 7.3-9.5). The pt with Fallopian tube cancer had a CR. DLTs with C 1 were seen in 2/6 evaluable pts at L1 (1 pt w/grade 3 hyponatremia and dehydration, and 1pt w/grade 4 thrombocytopenia [PLT]), leading to de-escalation of carb. At L2, 1 pt had grade 4 PLT. At L5, 1 pt had grade 4 PLT, and 2 pts grade 3 PLT (1 pt also experienced grade 4 granulocytopenia [ANC]), defining the MTD at carb AUC 5 and V 150 mg BID (L4). Dose delays and/or dose adjustments due to grade ≥ 2 toxicities for ANC or PLT were seen during the first 3 Cs at L1 (100%), L2 (50 %), L3 (67%), L4 (83 %), and at L5 (67%). Conclusions: The combination of carb and V is active, and is associated with substantial clinical benefit rate and managable hematologic toxicities in BRCA carriers with MBC. Further definition of the role of V is warranted.
| Dose levels | L1 | L2 | L3 | L4 MTD | L5 |
|---|---|---|---|---|---|
| Carb AUC | 6 | 5 | 5 | 5 | 5 |
| V in mg | 50 BID | 50 BID | 100 BID | 150 BID | 200 BID |
| # of pts | 7*^ | 6 | 3 | 6 | 6 |
| DLTs | 2 | 1 | 0 | 0 | 3 |
| # of Cs given | 9 (1-15) | 10 (1-12) | 12 (9-14) | 9+ (4-10+) | 7.5 (1-15+) |
* One pt ineligible/inevaluable (progressing pre-existing brain metastasis). ^ One pt ineligible (pathology: Fallopian tube cancer).
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Abstract Details
Session Type
Poster Discussion Session
Session Title
Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy
Track
Breast Cancer
Sub Track
Cytotoxic Chemotherapy
Citation
J Clin Oncol 31, 2013 (suppl; abstr 1024)
DOI
10.1200/jco.2013.31.15_suppl.1024
Abstract #
1024
Poster Bd #
16
Abstract Disclosures
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