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TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases

Publication ,  Journal Article
Anders, C; Deal, AM; Abramson, V; Liu, MC; Storniolo, AM; Carpenter, JT; Puhalla, S; Nanda, R; Melhem-Bertrandt, A; Lin, NU; Kelly Marcom, P ...
Published in: Breast Cancer Research and Treatment
January 1, 2014

Nearly half of patients with advanced triple negative breast cancer (TNBC) develop brain metastases (BM) and most will also have uncontrolled extracranial disease. This study evaluated the safety and efficacy of iniparib, a small molecule anti-cancer agent that alters reactive oxygen species tumor metabolism and penetrates the blood brain barrier, with the topoisomerase I inhibitor irinotecan in patients with TNBC-BM. Eligible patients had TNBC with new or progressive BM and received irinotecan and iniparib every 3 weeks. Time to progression (TTP) was the primary end point; secondary endpoints were response rate (RR), clinical benefit rate (CBR), overall survival (OS), toxicity, and health-related quality of life. Correlative endpoints included molecular subtyping and gene expression studies on pre-treatment archival tissues, and determination of germline BRCA1/2 status. Thirty-seven patients began treatment; 34 were evaluable for efficacy. Five of 24 patients were known to carry a BRCA germline mutation (4 BRCA1, 1 BRCA2). Median TTP was 2.14 months and median OS was 7.8 months. Intracranial RR was 12 %, while intracranial CBR was 27 %. Treatment was well-tolerated; the most common grade 3/4 adverse events were neutropenia and fatigue. Grade 3/4 diarrhea was rare (3 %). Intrinsic subtyping revealed 19 of 21 tumors (79 %) were basal-like, and intracranial response was associated with high expression of proliferation-related genes. This study suggests a modest benefit of irinotecan plus iniparib in progressive TNBC-BM. More importantly, this trial design is feasible and lays the foundation for additional studies for this treatment-refractory disease. © 2014 The Author(s).

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Published In

Breast Cancer Research and Treatment

DOI

EISSN

1573-7217

ISSN

0167-6806

Publication Date

January 1, 2014

Volume

146

Issue

3

Start / End Page

557 / 566

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Chicago
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Anders, C., Deal, A. M., Abramson, V., Liu, M. C., Storniolo, A. M., Carpenter, J. T., … Carey, L. A. (2014). TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Research and Treatment, 146(3), 557–566. https://doi.org/10.1007/s10549-014-3039-y
Anders, C., A. M. Deal, V. Abramson, M. C. Liu, A. M. Storniolo, J. T. Carpenter, S. Puhalla, et al. “TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases.” Breast Cancer Research and Treatment 146, no. 3 (January 1, 2014): 557–66. https://doi.org/10.1007/s10549-014-3039-y.
Anders C, Deal AM, Abramson V, Liu MC, Storniolo AM, Carpenter JT, et al. TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Research and Treatment. 2014 Jan 1;146(3):557–66.
Anders, C., et al. “TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases.” Breast Cancer Research and Treatment, vol. 146, no. 3, Jan. 2014, pp. 557–66. Scopus, doi:10.1007/s10549-014-3039-y.
Anders C, Deal AM, Abramson V, Liu MC, Storniolo AM, Carpenter JT, Puhalla S, Nanda R, Melhem-Bertrandt A, Lin NU, Kelly Marcom P, Van Poznak C, Stearns V, Melisko M, Smith JK, Karginova O, Parker J, Berg J, Winer EP, Peterman A, Prat A, Perou CM, Wolff AC, Carey LA. TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Research and Treatment. 2014 Jan 1;146(3):557–566.
Journal cover image

Published In

Breast Cancer Research and Treatment

DOI

EISSN

1573-7217

ISSN

0167-6806

Publication Date

January 1, 2014

Volume

146

Issue

3

Start / End Page

557 / 566

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences