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A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR-β

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Summary

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.

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Acknowledgements

This work was supported in part by the National Institutes of Health/National Cancer Institute (NCI P30 CA016672). Dr. Giordano is supported by CPRIT RP160674 and Komen SAC150061. Dr. Yam is supported by the Allison and Brian Grove Endowed Fellowship for Breast Medical Oncology, the Susan Papizan Dolan Fellowship in Breast Oncology, and the 2018 Gianni Bonadonna Breast Cancer Research Fellowship. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the sponsors.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, Dan L. Duncan Building (CPB5.3542), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354, Houston, TX, 77030, USA

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

  2. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gaiane M. Rauch & Wei Yang

  3. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Abenaa M. Brewster

  4. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Robert C. Bast Jr

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  1. Clinton Yam
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Yam, C., Murthy, R.K., Rauch, G.M. et al. A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR-β. Invest New Drugs 36, 1103–1109 (2018). https://doi.org/10.1007/s10637-018-0672-z

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