A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer.

Authors:
  • SIS. J. Isakoff
    S. J. Isakoff
  • BOB. Overmoyer
    B. Overmoyer
  • NTN. M. Tung
    N. M. Tung
  • RGR. S. Gelman
    R. S. Gelman
  • VGV. L. Giranda
    V. L. Giranda
  • KBK. M. Bernhard
    K. M. Bernhard
  • KHK. R. Habin
    K. R. Habin
  • LEL. W. Ellisen
    L. W. Ellisen
  • EWE. P. Winer
    E. P. Winer
  • PGP. E. Goss
    P. E. Goss
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Abstract
1019 Background: Veliparib (ABT-888) is a novel oral inhibitor of Poly (ADP-Ribose) Polymerase (PARP) 1 and 2. Veliparib and temozolomide (TMZ) are synergistic in breast cancer xenograft models. TMZ has minimal activity in breast cancer likely due to robust repair methylated DNA adducts by the base excision repair (BER) pathway and MGMT. We hypothesized that combining veliparib with TMZ would be active in metastatic breast cancer (MBC). Methods: We conducted a single arm phase II trial of veliparib and TMZ in 41 MBC patients (pts). Eligibility included measurable MBC, >1 prior MBC therapy, and PS ≤ 2; previously treated stable brain metastases were allowed. Available archived tumor samples were collected. The initial Simon 2 stage design was modified to a single stage (n=41) due to rapid accrual. Patients received veliparib (40 mg PO BID days 1-7) and TMZ (150mg/m2 PO QD days 1-5) on a 28 day cycle. After higher than expected grade 4 thrombocytopenia was observed, the dose of veliparib was reduced to 30 m...