Reference Detail

Ref Type Journal Article
PMID (26801247)
Authors Rodler ET, Kurland BF, Griffin M, Gralow JR, Porter P, Yeh RF, Gadi VK, Guenthoer J, Beumer JH, Korde L, Strychor S, Kiesel BF, Linden HM, Thompson JA, Swisher E, Chai X, Shepherd S, Giranda V, Specht JM
Title 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.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 22
Issue 12
Date 2016 Jun 15
URL
Abstract Text 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 progression-free survival [PFS; 10 of 14 (71%) vs. 8 of 27 (30%), mid-P = 0.01]. Median PFS for all 50 patients was 5.5 months (95% confidence interval, 4.1-6.7).Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates. A phase II randomized trial is planned to assess veliparib's contribution to cisplatin chemotherapy in metastatic TNBC and BRCA mutation-associated breast cancer. Clin Cancer Res; 22(12); 2855-64. ©2016 AACR.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRCA1 mutant Her2-receptor negative breast cancer sensitive Cisplatin + Veliparib + Vinorelbine Phase I Actionable In a Phase I trial, Veliparib (ABT-888), in combination with Platinol (cisplatin) and Navelbine (vinorelbine), resulted in a greater complete response (7%, 1/14), partial response (50%, 7/14), and 6-month progression free survival rate (71%, 10/14) in Erbb2 (Her2) negative breast cancer patients harboring germline BRCA1 or BRCA2 mutations compared to BRCA wild-type patients (PMID: 26801247). 26801247
BRCA2 mutant Her2-receptor negative breast cancer predicted - sensitive Cisplatin + Veliparib + Vinorelbine Phase I Actionable In a Phase I trial, Veliparib (ABT-888) in combination with Platinol (cisplatin) and Navelbine (vinorelbine) resulted in a greater complete response (7%, 1/14), partial response (50%, 7/14), and 6-month progression free survival rate (71%, 10/14) in Erbb2 (Her2) negative breast cancer patients harboring germline BRCA1 or BRCA2 mutations compared to BRCA wild-type patients (PMID: 26801247). 26801247
Unknown unknown Her2-receptor negative breast cancer not applicable Cisplatin + Veliparib + Vinorelbine Phase I Actionable In a Phase I trial, Veliparib (ABT-888) in combination with Platinol (cisplatin) and Navelbine (vinorelbine) resulted in a complete response in 4% (2/48), partial response in 31% (15/48), and stable disease in 44% (31/48) of patients with Erbb2 (Her2) negative breast cancer (PMID: 26801247). 26801247