Phase II studies of two different schedules of dasatinib in bone metastasis predominant metastatic breast cancer: SWOG S0622
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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.
KeywordsBreast cancer Phase II clinical trial Bone metastasis Tyrosine kinase inhibitors Dasatinib
This work was supported by the National Institutes of Health/National Cancer Institute/National Clinical Trials Network grants CA180888, CA180819, CA180801, CA180834, CA180846; National Institutes of Health/National Cancer Institute Community Oncology Research Program grants CA189971, CA189830, CA189872, CA189954, CA189952, CA189858, CA189856, CA189817, CA190002; National Institutes of Health/National Cancer Institute legacy Grants CA35158, CA35119, CA11083, CA76448, CA04919, CA46282, CA76447, CA22433, CA16385; and in part by the Bristol-Myers Squibb and Janssen Diagnostics Corporation. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Institute of Health or Bristol-Myers Squibb and Janssen Diagnostics Corporation.
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Conflict of interest
William E. Barlow, Evan T. Keller, Gabriel N. Hortobagyi, Jill M. Keller, Danika L. Lew, Carol M. Moinpour, Philip A. Dy, Anne F. Schott declare no conflict of interest; Catherine H. Van Poznak reports sponsorship of clinical trial to institution by the Bayer Pharmaceuticals; Daniel F. Hayes 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, the 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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