Veliparib, an orally administered poly(ADP-ribose) polymerase (PARP) inhibitor, is under evaluation in Phase I-III clinical trials, including Phase III studies for non-small-cell lung cancer, ovarian cancer, and breast cancer. A Phase II trial is investigating whether adding veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation.
Rationale for Veliparib in BRCA-Mutated Breast Cancer
Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and PARP inhibitors. This sensitivity forms the basis for exploring veliparib's potential in treating BRCA-mutated breast cancer. The trial (EudraCT 2011-002913-12, NCT01506609) aims to assess whether veliparib can enhance the effects of standard chemotherapy regimens in this specific patient population.
Trial Design and Objectives
The Phase II trial is designed to evaluate the efficacy and safety of veliparib in combination with either temozolomide or carboplatin/paclitaxel. The primary objective is to determine if the addition of veliparib improves clinical outcomes compared to chemotherapy alone. Secondary endpoints may include progression-free survival, overall survival, and response rates. The study includes patients with locally recurrent or metastatic breast cancer who have confirmed deleterious BRCA1 or BRCA2 germline mutations.
