Significance of tyrosine kinase inhibitors in the treatment of metastatic breast cancer

Mundhenke C, Strauss A, Schem C (2009)

Publication Type: Journal article, Review article

Publication year: 2009

Journal

Breast Care Karger

Book Volume: 4

Pages Range: 373-378

Journal Issue: 6

DOI: 10.1159/000261705

Abstract

Preclinical and clinical trials suggest that tyrosine kinase inhibitors (TKI) could supplement current therapies in metastatic breast cancer (MBC). HER-2 inhibition is still a main focus. Numerous agents targeting the epidermal growth factor receptors EGFR and HER-2 are currently tested after previous trastuzumab treatment. Lapatinib targets HER-2 and EGFR. As monotherapy, clinical activity was low. Combined with cytotoxic agents, lapatinib showed good activity (overall response rate (ORR) 24-27%) and moderate toxicity. Neratinib, a pan-ErbB TKI, showed an ORR of 26%. Neratinib combined with trastzumab was well tolerated and active (ORR = 27%). After bevacizumab's proof-of-concept studies, antiang-iogenesis remains of importance. Sunitinib inhibits the vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor (PDGFR), c-kit and the colony-stimulating factor 1 (CSF-1) receptor. Monotherapy is tolerated and moderately active in MBC. Combination trials are ongoing. Toxicities of docetaxel ± sunitinib were manageable (ORR 72.2%). Pazopanib tar-gets VEGFR, PDGFR and c-kit. Pazopanib ± lapatinib was superior in combination (progression-free survival (PFS) = 27% vs. 19%). Axitinib has similar targets. Combined with docetaxel, it was superior compared to placebo (ORR 40% vs. 23%), with manageable toxicity. Imatinib inhibits PDGFR and c-kit. As monotherapy, it showed no clinical activity. Combination trials with chemotherapy are ongoing. © 2009 S. Karger GmbH, Freiburg.

Authors with CRIS profile

Christoph Mundhenke

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Mundhenke, C., Strauss, A., & Schem, C. (2009). Significance of tyrosine kinase inhibitors in the treatment of metastatic breast cancer. Breast Care, 4(6), 373-378. https://doi.org/10.1159/000261705

MLA:

Mundhenke, Christoph, Alexander Strauss, and Christian Schem. "Significance of tyrosine kinase inhibitors in the treatment of metastatic breast cancer." Breast Care 4.6 (2009): 373-378.

BibTeX: Download