Bosutinib in Combination With the Aromatase Inhibitor Exemestane: A Phase II Trial in Postmenopausal Women With Previously Treated Locally Advanced or Metastatic Hormone Receptor‐Positive/HER2‐Negative Breast Cancer |
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| Authors: | Beverly Moy Patrick Neven Fabienne Lebrun Meritxell Bellet Binghe Xu Tomasz Sarosiek Louis Chow Paul Goss Charles Zacharchuk Eric Leip Kathleen Turnbull Nathalie Bardy‐Bouxin Ladan Duvillié István Láng |
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| Affiliation: | 1. Massachusetts General Hospital, Boston, Massachusetts, USA;2. UZ Leuven, Leuven, Belgium;3. Institute Jules Bordet, Brussels, Belgium;4. Vall d'Hebron University Hospital, Barcelona, Spain;5. Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China;6. Centrum Medyczne Ostrobramska NZOZ MAGODENT, Warszawa, Poland;7. Unimed Medical Institute, Comprehensive Centre for Breast Diseases, Hong Kong, People's Republic of China;8. Pfizer Inc, Cambridge, Massachusetts, USA;9. Pfizer Global Research and Development, Paris, France;10. Országos Onkológiai Intézet, Budapest, Hungary |
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| Abstract: | Background.Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as second-line therapy in previously treated hormone receptor-positive (HR+) locally advanced or metastatic BC.Methods.This was a phase II study with patients enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and initial efficacy was assessed. After the lead-in and dose-determination phase, randomized evaluation of combination therapy versus exemestane was planned.Results.Thirty-nine of 42 patients (93%) experienced treatment-related AEs including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy’s law criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on treatment discontinuation. One patient (300 mg/day) achieved confirmed partial response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease for >24 weeks; a best response of progressive disease occurred in 15 of 42 patients (36%). Median progression-free survival was 12.3 weeks (80% confidence interval: 11.0–15.6).Conclusion.The risk-benefit profile of bosutinib at 300 mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC. |
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