Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer

Lapatinib is an oral dual tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2), both frequently overexpressed in human cancer. Preclinical data have shown that lapatinib is a potent and selective inhibitor of the tyrosine kinase domain of EGFR and HER2, and tumor cells that overexpress these receptors are growth inhibited by lapatinib both in vitro and in vivo. Phase I clinical trials have shown that lapatinib is well tolerated, with mild diarrhea and rash the most frequent toxicities, and early evidence of clinical efficacy has been reported especially in HER2-positive breast cancer. Phase II studies have shown activity for lapatinib in trastuzumab-refractory breast cancer either alone or in combination with trastuzumab. When used as first-line monotherapy for advanced breast cancer, objective tumor responses have been seen in 28% of patients with untreated HER2-positive advanced breast cancer. An extensive phase III program in advanced breast cancer is now in progress both for refractory disease and as first-line therapy in combination with chemotherapy with and without trastuzumab, and with endocrine therapy. Phase II studies have also been conducted in a variety of other tumors, including renal cell cancer. Parallel biomarker studies are starting to elucidate predictive molecular phenotypes that may indicate likelihood of response to lapatinib, and these may direct future trials with this oral tyrosine kinase inhibitor.