Riely GJ et al. - In an overview of 3 representative second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), the preliminary results from phase I and phase II trials for BIBW-2992 and XL647 are discussed Methods
A small number of pts with EGFR mutations have primary resistance to erlotinib and gefitinib, and most pts who initially respond to treatment with erlotinib or gefitinib will develop resistance to first-generation EGFR TKIs
The problems with both primary and acquired resistance to erlotinib and gefitinib support the need for development of additional agents that inhibit EGFR signaling
Results
HKI-272 has completed accrual of a phase II trial in both untreated pts and pts with acquired resistance to erlotinib or gefitinib
XL647 is a reversible inhibitor of EGFR, HER2, and vascular epidermal growth factor receptor
Preclinical work shows that XL647 can inhibit cell lines bearing mutated forms of EGFR that have been associated with acquired resistance
BIBW2992 is an irreversible EGFR TKI that also inhibits HER2 and vascular epidermal growth factor receptors
In vitro work shows that this compound inhibits wild-type EGFR, EGFR exon 19 deletion, EGFR L858R, and EGFR T790M, the mutation associated with acquired resistance
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