Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Eve T RodlerJennifer Specht

Abstract

Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) and BRCA mutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine. A 3+3 dose-escalation design evaluated veliparib administered twice daily for 14 days with cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1, 8) every 21 days, for 6 to 10 cycles, followed by veliparib monotherapy. Pharmacokinetics, measurement of poly(ADP-ribose) in peripheral blood mononuclear cells, and preliminary efficacy were assessed. IHC and gene-expression profiling were evaluated as potential predictors of response. Forty-five patients enrolled in nine dose cohorts plus five in an expansion cohort at the highest dose level and recommended phase II dose, 300 mg twice daily. The MTD of veliparib was not reached. Neutropenia (36%), anemia (30%), and thrombocytopenia (12%) were the most common grade 3/4 adverse events. Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%). Germline BRCA mutation presence versus absence was associated with 6-month pro...Continue Reading

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