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, I. Láng

Research output: Contribution to journalArticle

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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 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
JournalOncologist
Volume19
Issue number4
DOIs
Publication statusPublished - 2014

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exemestane
Aromatase Inhibitors
Hormones
Breast Neoplasms
Therapeutics
src-Family Kinases
bosutinib
Disease-Free Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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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. / Moy, Beverly; Neven, Patrick; Lebrun, Fabienne; Bellet, Meritxell; Xu, Binghe; Sarosiek, Tomasz; Chow, Louis; Goss, Paul; Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen; Bardy-Bouxin, Nathalie; Duvillié, Ladan; Láng, I.

In: Oncologist, Vol. 19, No. 4, 2014, p. 346-347.

Research output: Contribution to journalArticle

Moy, Beverly ; Neven, Patrick ; Lebrun, Fabienne ; Bellet, Meritxell ; Xu, Binghe ; Sarosiek, Tomasz ; Chow, Louis ; Goss, Paul ; Zacharchuk, Charles ; Leip, Eric ; Turnbull, Kathleen ; Bardy-Bouxin, Nathalie ; Duvillié, Ladan ; Láng, I. / 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. In: Oncologist. 2014 ; Vol. 19, No. 4. pp. 346-347.
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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 300mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC.",
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AU - Neven, Patrick

AU - Lebrun, Fabienne

AU - Bellet, Meritxell

AU - Xu, Binghe

AU - Sarosiek, Tomasz

AU - Chow, Louis

AU - Goss, Paul

AU - Zacharchuk, Charles

AU - Leip, Eric

AU - Turnbull, Kathleen

AU - Bardy-Bouxin, Nathalie

AU - Duvillié, Ladan

AU - Láng, I.

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