A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR-ß.
Invest New Drugs
; 36(6): 1103-1109, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-30311036
ABSTRACT
Background Imatinib mesylate is a potent inhibitor of the Abl, KIT and platelet derived growth factor (PDGF) receptor tyrosine kinases. Preclinical data suggest that combining imatinib mesylate with anti-estrogen therapy may be synergistic in hormone receptor-positive breast cancer. We report results of the first phase II trial evaluating the efficacy of the novel combination of imatinib mesylate and letrozole in the treatment of postmenopausal women with metastatic breast cancer. Patients and Methods 45 postmenopausal women with hormone receptor-positive metastatic breast cancer whose tumors demonstrated c-kit and/or PDGFR-ß positivity were treated with imatinib mesylate 400 mg PO twice daily and letrozole 2.5 mg PO once daily until disease progression or unacceptable toxicity. Results There were no complete responses and five partial responses for an objective response rate of 11%. An additional 16 patients had stable disease lasting at least 24 weeks for a clinical benefit rate of 46.7%. The median progression-free and overall survival was 8.7 months (95% confidence interval 3.8-11.4 months) and 44.3 months (95% confidence interval 34.0-55.3 months), respectively. The most common grade 3 or higher treatment related adverse events were fatigue and diarrhea, occurring in 9 (20%) and 7 patients (16%), respectively. Conclusion The combination of imatinib mesylate and letrozole is well tolerated but appears to have limited efficacy in the treatment of hormone receptor-positive metastatic breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
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Proto-Oncogene Proteins c-kit
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Receptor, Platelet-Derived Growth Factor beta
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Imatinib Mesylate
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Letrozole
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Language:
En
Journal:
Invest New Drugs
Year:
2018
Type:
Article
Affiliation country:
United States