title: Phase II studies of two different schedules of dasatinib in bone metastasis predominant metastatic breast cancer: SWOG S0622.
abstract: 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.
authors.affiliation: University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA. aschott@umich.edu.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Schott
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.affiliation: University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Van Poznak
authors.affiliation: University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Moinpour
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Lew
authors.affiliation: Heartland Cancer Research NCORP, Crossroads Cancer Center, Effingham, IL, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Dy
authors.affiliation: University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.affiliation: University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Keller
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069439:Dasatinib / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000069439:Dasatinib
keywords: Bone metastasis; Breast cancer; Dasatinib; Phase II clinical trial; Tyrosine kinase inhibitors