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Breast Cancer Res Treat. 2016 Aug;159(1):87-95. doi: 10.1007/s10549-016-3911-z. Epub 2016 Jul 30.

Phase II studies of two different schedules of dasatinib in bone metastasis predominant metastatic breast cancer: SWOG S0622.

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University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
SWOG Statistical Center, Seattle, WA, USA.
University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Heartland Cancer Research NCORP, Crossroads Cancer Center, Effingham, IL, USA.
University of Texas MD Anderson Cancer Center, Houston, TX, USA.


Bone metastases from breast cancer are common, causing significant morbidity. Preclinical data of dasatinib, an oral small molecule inhibitor of multiple oncogenic tyrosine kinases, suggested efficacy in tumor control and palliation of bone metastases in metastatic breast cancer (MBC). This clinical trial aimed to determine whether treatment with either of 2 dose schedules of dasatinib results in a progression-free survival (PFS) >50 % at 24 weeks in bone metastasis predominant MBC, to evaluate the toxicity of the 2 dosing regimens, and explore whether treatment results in decreased serum bone turnover markers and patient-reported "worst pain." Subjects with bone metastasis predominant MBC were randomly assigned to either 100 mg of dasatinib once daily, or 70 mg twice daily, with treatment continued until time of disease progression or intolerable toxicity. Planned accrual was 40 patients in each arm. The primary trial endpoint was PFS, defined as time from registration to progression or death due to any cause. Median PFS for all eligible patients (79) was 12.6 weeks (95 % CI 9.1-16.7). Neither cohort met the threshold for further clinical interest. There were no significant differences in PFS by randomized treatment arm (p = 0.85). Toxicity was similar in both cohorts, with no clear trend in serum biomarkers of bone turnover or patient-reported pain. Dasatinib was ineffective in controlling bone-predominant MBC in a patient population, unselected by molecular markers. Further study of dasatinib in breast cancer should not be pursued unless performed in molecularly determined patient subsets, or rational combinations.


Bone metastasis; Breast cancer; Dasatinib; Phase II clinical trial; Tyrosine kinase inhibitors

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Conflict of interest statement

None: WB, EK, GH, JK, DL, CM, PD, AS; CV reports sponsorship of clinical trial to institution by Bayer Pharmaceuticals; DH reports Stock Ownership: Oncimmune LLC, De Soto, KS, USA – stock options (7/20/09), Inbiomotion, Barcelona, Spain – stock options (10/22/12); Lecture/Honorarium: Visiting Consultant for Lilly Oncology, Indianapolis, IN (11/7/14); Sponsored Clinical Research – Principle or co-Investigator: Merrimack Pharmaceuticals, Inc. (Parexel Intl Corp) (01/24/15-02/02/20), Eli Lilly Company (06/19/15-04/30/19), Janssen R&D, LLC (Johnson & Johnson) (12/23/08-04/28/18), Puma Biotechnology, Inc., (subcontract Wash Univ St. Louis to Univ Mich) (07/19/13-07/31/18), Pfizer (07/22/13-07/14/18), Astra Zeneca (11/01/14-10/31/16), Astra Zeneca (02/06/15-02/05/16; Royalties from licensed technology: Janssen R&D, LLC (Johnson & Johnson) (08/01/14); Patents: Title: A method for predicting progression free and overall survival at each follow-up timepoint during therapy of metastatic breast cancer patients using circulating tumor cells. Filed 14 Mar 2005 with the European Patent Office, Netherlands. Application No./Patent No. 05725638.0-1223-US2005008602. Applicant/Proprietor: Immunicon Corporation. Dr. Daniel F. Hayes is designated as inventor/co-inventor; Title: Diagnosis and Treatment of Breast Cancer. Patent No.: US 8,790,878 B2. Date of Patent: Jul. 29, 2014. Applicant Proprietor: University of Michigan. Dr. Daniel F. Hayes is designated as inventor/co-inventor; Title: Circulating Tumor Cell Capturing Techniques and Devices. Patent No.: US 8,951,484 B2. Date of Patent: Feb. 10, 2015. Applicant Proprietor: University of Michigan. Dr. Daniel F. Hayes is designated as inventor/co-inventor.

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