Approximately 20% of new diagnosed breast
cancers overexpress the
human epidermal growth factor receptor 2 (EGFR2), also known as erythroblastic
leukemia viral oncogene homolog 2 (ERBB2)
protein, as a consequence of ERBB2 gene amplification, resulting in a poor prognosis. Clinical outcome can be substantially improved by ERBB2-targeted
therapy.
Lapatinib is a potent, orally bioavailable small molecule that reversibly and selectively inhibits
epidermal growth factor receptor (EGFR1 or ERBB1) and ERBB2
tyrosine kinases.
Lapatinib binds the
adenosine triphosphate-binding site of the receptor's intracellular domain to inhibit
tumor cell growth. This review summarizes the pharmacology, pharmacokinetics, efficacy, and tolerability of
lapatinib, and reviews both Food and Drug Administration-approved and investigational uses of
lapatinib in
breast cancer therapy. The
drug is generally well tolerated in patients, with
diarrhea and rashes being the most common (usually mild or moderate) adverse effects. Unlike
trastuzumab,
lapatinib has infrequent adverse effects on cardiac function.
Lapatinib has substantial activity for advanced ERBB2-positive
breast cancer, particularly in combination with
capecitabine, following progression after
anthracyclines,
taxanes, and
trastuzumab.
Lapatinib combined with
capecitabine yielded significant improvements in time to progression and response rate compared with
capecitabine alone. This
drug can also be combined with
letrozole for the treatment of postmenopausal women with ERBB2-positive
breast cancer, for whom hormonal
therapy is indicated.
Lapatinib has shown early promise in treatment of central nervous system
metastasis and is being further evaluated in various clinical settings.