Bosutinib in Combination With the Aromatase Inhibitor Letrozole: A Phase II Trial in Postmenopausal Women Evaluating First‐Line Endocrine Therapy in 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.Endocrine therapy resistance in hormone receptor-positive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2− BC.Methods.Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy.Results.Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy’s law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2.Conclusion.The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole. |
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