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

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

Research output: Article

6 Citations (Scopus)


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 300mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC.

Original languageEnglish
Pages (from-to)346-347
Number of pages2
Issue number4
Publication statusPublished - 2014


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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