M Campone1, I Bondarenko2, S Brincat3, Y Hotko4, P N Munster5, E Chmielowska6, P Fumoleau7, R Ward8, N Bardy-Bouxin9, E Leip10, K Turnbull10, C Zacharchuk10, R J Epstein11. 1. Department of Medical Oncology, Centre René Gauducheau, Nantes Saint-Herblain; UMR 892 INSERM, Nantes, France. Electronic address: m-campone@nantes.fnclcc.fr. 2. Department of Oncology and Medical Radiology, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine. 3. Radiotherapy and Oncology Department, Sir Paul Boffa Hospital, Floriana, Malta. 4. Transcarpathian Regional Clinical Oncology Dispensary, Uzhgorod National University, Uzhgorod, Ukraine. 5. Departments of Breast and Experimental Therapeutics, H. Lee Moffitt Cancer Center, Tampa, USA. 6. Multi-Med Salata i Wsp sp. Jawna, Lodz, Poland. 7. Department of Oncology, Centre Georges-François Leclerc, Dijon, France. 8. Department of Medical Oncology, Vincent's Hospital, Darlinghurst, Australia. 9. Pfizer Inc, Paris, France. 10. Pfizer Inc, Cambridge, USA. 11. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong-Kong.
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.
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.
Authors: Tapasree Roy Sarkar; Shikha Sharan; Jun Wang; Snehalata A Pawar; Carrie A Cantwell; Peter F Johnson; Deborah K Morrison; Ju-Ming Wang; Esta Sterneck Journal: Mol Cell Biol Date: 2011-10-28 Impact factor: 4.272