Lapatinib: a dual tyrosine kinase inhibitor for metastatic breast cancer

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug and food interactions, dosage and administration, and role in therapy of lapatinib in metastatic breast cancer are reviewed.

Lapatinib is a small-molecule tyrosine kinase inhibitor that dually targets human epidermal growth factor receptors 1 and 2 (HER2). Unlike trastuzumab, lapatinib enters the cell and binds to the intracellular domain of the tyrosine kinase receptor, allowing for complete blockage of the autophosphorylation reaction and a complete halt to the downstream cascade of events. After oral administration, lapatinib reaches peak plasma levels within approximately 4 hours, steady-state levels within six to seven days, and has a half-life of 24 hours. Combination therapy with lapatinib and capecitabine has demonstrated superior time to progression compared with capecitabine monotherapy for the treatment of HER2-positive metastatic breast cancer refractory to anthracycline-, taxane-, and trastuzumab-containing regimens. Unlike trastuzumab, lapatinib is an orally active agent with promising clinical activity in metastatic breast cancer and is associated with a better adverse-effect profile. The most frequently reported adverse events in patients receiving combination therapy with lapatinib and capecitabine were diarrhea and hand-foot syndrome. Ongoing research has further evaluated the safety of lapatinib regarding cardiac effects and found that the majority of left ventricular ejection fraction decreases from baseline were asymptomatic and reversible.

Lapatinib has demonstrated efficacy in combination with capecitabine in patients with previously treated HER2-positive metastatic breast cancer. In patients with metastatic disease refractory to trastuzumab-, anthracycline-, and taxane-containing regimens, the addition of lapatinib to capecitabine may extend the time to disease progression and progression-free survival.