1. Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy
- Author
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Kathleen Turnbull, Richard J. Epstein, Stephen Brincat, Pierre Fumoleau, Mario Campone, Yevhen Hotko, Pamela N. Munster, E. Chmielowska, Charles Zacharchuk, Igor Bondarenko, Eric Leip, R. Ward, and Nathalie Bardy-Bouxin
- Subjects
Oncology ,Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Phases of clinical research ,Antineoplastic Agents ,Breast Neoplasms ,Kaplan-Meier Estimate ,Disease-Free Survival ,Metastasis ,Protein-tyrosine kinase -- Inhibitors -- Therapeutic use ,Internal medicine ,Nitriles ,medicine ,Humans ,Neoplasm Metastasis ,education ,Survival rate ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Salvage Therapy ,Chemotherapy ,education.field_of_study ,Aniline Compounds ,Breast -- Cancer -- Treatment ,business.industry ,Breast -- Cancer -- Case studies ,Hematology ,Middle Aged ,Protein-Tyrosine Kinases ,medicine.disease ,Chemotherapy regimen ,Metastatic breast cancer ,Dasatinib ,Breast -- Tumors -- Chemotherapy ,Quinolines ,Female ,Bone Remodeling ,business ,Bosutinib ,medicine.drug - Abstract
Background: This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. Patients and methods: Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. Results: Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. Conclusions: Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population., peer-reviewed
- Published
- 2011