A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-12

AUTHORS

Clinton Yam, Rashmi K. Murthy, Gaiane M. Rauch, James L. Murray, Ronald S. Walters, Vicente Valero, Abenaa M. Brewster, Robert C. Bast, Daniel J. Booser, Sharon H. Giordano, Francisco J. Esteva, Wei Yang, Gabriel N. Hortobagyi, Stacy L. Moulder, Banu Arun

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-β 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. More... »

PAGES

1-7

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-018-0672-z

DOI

http://dx.doi.org/10.1007/s10637-018-0672-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107541599

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30311036


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    "description": "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-\u03b2 positivity were treated with imatinib mesylate 400\u00a0mg PO twice daily and letrozole 2.5\u00a0mg 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\u00a0weeks for a clinical benefit rate of 46.7%. The median progression-free and overall survival was 8.7\u00a0months (95% confidence interval: 3.8-11.4\u00a0months) and 44.3\u00a0months (95% confidence interval: 34.0-55.3\u00a0months), 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.", 
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