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TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis.

Publication ,  Journal Article
Mitri, Z; Nanda, R; Blackwell, K; Costelloe, CM; Hood, I; Wei, C; Brewster, AM; Ibrahim, NK; Koenig, KB; Hortobagyi, GN; Van Poznak, C ...
Published in: Clin Cancer Res
December 1, 2016

PURPOSE: Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases. EXPERIMENTAL DESIGN: A 3+3 lead in phase I design confirmed the RP2D allowing activation of the single-arm, phase II trial. Zoledronic acid was administered intravenously on day 1, and dasatinib was given orally once daily for 28 days each cycle as twice daily administration caused dose-limiting toxicity (DLT). Response was assessed every three cycles. N-telopeptide (NTx) was serially measured. RESULTS: A total of 25 patients were enrolled. No DLTs were noted at the RP2D of dasatinib = 100 mg/d. Common adverse events were grade 1-2: rash (9/25, 36%), fatigue (9/25, 36%), pain (9/25, 36%), nausea (6/25, 20%). The objective response rate in bone was 5/22 (23%), all partial responses (PR). The clinical benefit rate [PRs + stable disease (SD) ≥ 6 months] in bone was 8/22 (36%). Median time to treatment failure was 2.70 months [95% confidence interval (CI), 1.84-5.72] in the general cohort, 3.65 months (95% CI, 1.97-7.33) in patients with hormone receptor (HR)-positive breast cancer and 0.70 months (95% CI, 0.30-NA) in those with HR-negative disease. Factors associated with response in bone included lower tumor grade, HR-positive status, and pretreatment high NTx levels. CONCLUSIONS: Combination therapy was well tolerated and produced responses in bone in patients with HR-positive tumors. Clin Cancer Res; 22(23); 5706-12. ©2016 AACR.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

December 1, 2016

Volume

22

Issue

23

Start / End Page

5706 / 5712

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Zoledronic Acid
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Middle Aged
  • Imidazoles
  • Humans
  • Female
  • Diphosphonates
 

Citation

APA
Chicago
ICMJE
MLA
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Mitri, Z., Nanda, R., Blackwell, K., Costelloe, C. M., Hood, I., Wei, C., … Translational Breast Cancer Research Consortium, . (2016). TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis. Clin Cancer Res, 22(23), 5706–5712. https://doi.org/10.1158/1078-0432.CCR-15-2845
Mitri, Zahi, Rita Nanda, Kimberly Blackwell, Colleen M. Costelloe, Ilona Hood, Caimiao Wei, Abenaa M. Brewster, et al. “TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis.Clin Cancer Res 22, no. 23 (December 1, 2016): 5706–12. https://doi.org/10.1158/1078-0432.CCR-15-2845.
Mitri Z, Nanda R, Blackwell K, Costelloe CM, Hood I, Wei C, et al. TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis. Clin Cancer Res. 2016 Dec 1;22(23):5706–12.
Mitri, Zahi, et al. “TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis.Clin Cancer Res, vol. 22, no. 23, Dec. 2016, pp. 5706–12. Pubmed, doi:10.1158/1078-0432.CCR-15-2845.
Mitri Z, Nanda R, Blackwell K, Costelloe CM, Hood I, Wei C, Brewster AM, Ibrahim NK, Koenig KB, Hortobagyi GN, Van Poznak C, Rimawi MF, Moulder-Thompson S, Translational Breast Cancer Research Consortium. TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis. Clin Cancer Res. 2016 Dec 1;22(23):5706–5712.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

December 1, 2016

Volume

22

Issue

23

Start / End Page

5706 / 5712

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Zoledronic Acid
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Middle Aged
  • Imidazoles
  • Humans
  • Female
  • Diphosphonates