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Oncologist. 2014 Apr;19(4):346-7. doi: 10.1634/theoncologist.2014-0022. Epub 2014 Mar 27.

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.

Author information

1
Massachusetts General Hospital, Boston, Massachusetts, USA;

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00793546.

PMID:
24674873
PMCID:
PMC3983831
DOI:
10.1634/theoncologist.2014-0022
[Indexed for MEDLINE]
Free PMC Article

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