title: A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale.
abstract: Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and 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 poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of 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 (Trial registration: EudraCT 2011-002913-12, NCT01506609).
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Isakoff
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Puhalla
authors.affiliation: Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.affiliation: Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, NSW 2031, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.affiliation: Department of General Oncology, Chaim Sheba Medical Center, Ramat Gan 52 621, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10022, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.affiliation: Department of Medical Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Telli
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris 75248, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.affiliation: The Center for Women's Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.affiliation: AbbVie Inc., Chicago, IL 60064, USA.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Johnson
authors.affiliation: AbbVie Inc., Chicago, IL 60064, USA.
authors.forename: David
authors.initials: D
authors.lastname: Maag
authors.affiliation: AbbVie Inc., Chicago, IL 60064, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: AbbVie Inc., Chicago, IL 60064, USA.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Giranda
authors.affiliation: AbbVie Inc., Chicago, IL 60064, USA.
authors.forename: Stacie P
authors.initials: SP
authors.lastname: Shepherd
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002985:Clinical Protocols; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015233:Models, Statistical; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D012107:Research Design; D018401:Sample Size; D000077204:Temozolomide
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001562:Benzimidazoles; C521013:veliparib; D003606:Dacarbazine; D016190:Carboplatin; D017239:Paclitaxel; D000077204:Temozolomide
keywords: BRCA1; BRCA2; DNA damage; PARP; PARP inhibitor; PARP trapping; breast cancer; synthetic lethality; veliparib