Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer

Abstract

Purpose: This review aims to present the preclinical and clinical data regarding efficacy and safety of lapatinib alone and in combination with other agents in the treatment of human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer. Background: HER2-positive (HER2+) breast cancer remains a treatment challenge. It is more aggressive than other breast cancers and it is associated with a poor outcome. Targeted therapy for HER2+ breast cancer has significantly changed the clinical course of the disease. Despite advances in therapy, there remains an unmet need in the treatment of HER2+ breast cancer. Lapatinib is a novel, orally bioavailable epidermal growth factor receptor/HER2+ targeted agent. Many trials have investigated the efficacy and safety of lapatinib alone and in conjunction with other agents in the treatment of HER2+ breast cancer. Methods and results: Preclinical and clinical trials of lapatinib have shown that it is effective in the treatment on HER2+ breast cancer. More important, studies show that it is effective in the setting of trastuzumab resistance and in the treatment of central nervous system metastases, both of which are current treatment challenges. Furthermore, lapatinib is effective in conjunction with trastuzumab in the treatment of early breast cancer. Data regarding the safety of lapatinib show that it is generally well tolerated; however, multiple studies have shown significant (grade 3 and 4) diarrhea and rash associated with lapatinib, thereby limiting its use. Carditoxicity has not been a significant adverse event associated with the use of lapatinib. Conclusion: Lapatinib is effective alone and in conjunction with other agents in the treatment of HER2+ breast cancer. However, its use is limited by significant diarrhea and rash.

Effects of lapatinib and trastuzumab on vascular endothelial growth factor in experimental corneal neovascularization

“…Upregulation of insulin‐like growth factor due to HER2 inhibition is one of the mechanisms of resistance to trastuzumab. The pathways activated by this upregulation were inhibited by lapatinib . In our study, we demonstrated that corneal NV was significantly regressed with lapatinib compared with trastuzumab.…”

“…demonstrated that treatment with a drug that selectively inhibits EGFR tyrosine phosphorylation led to a reduction of VEGF mRNA to 50% of the control level, which confirms that EGFR kinase activity influences VEGF mRNA regulation . In vitro studies have demonstrated that lapatinib inhibits both HER1 and HER2 and that lapatinib alone is more effective than HER1 blockers …”

“…In recent studies, it was also demonstrated that EGFR regulates VEGF expression and also that angiogenesis might be prevented with EGFR inhibitors. 23,[31][32][33][34][35][36][37] Human EGFR-2 is another receptor from EGFR family that is also affected by lapatinib. Trastuzumab only affects this receptor.…”

“…38 In vitro studies have demonstrated that lapatinib inhibits both HER1 and HER2 and that lapatinib alone is more effective than HER1 blockers. [32][33][34][35][36] Trastuzumab, a humanized monoclonal antibody specifically targeted against the extracellular domain of the HER2, is currently widely used in the treatment of HER2 -overexpressing early or metastatic breast cancer. The HER2 is a member of the EGFR family of receptor tyrosine kinases.…”

Lapatinib in patients with metastatic breast cancer following initial treatment with trastuzumab: an economic analysis from the Brazilian public health care perspective

“…Furthermore, since ongoing research into the use of lapatinib as a single option or in conjunction with other agents has found benefit for these patients, an even greater advantage would be created. 34,35 That is, on the equity side, an oral HER2-positive agent used alone or in combination with other therapies would obviate the need for intravenous administration, could be administered on an outpatient basis, and deliver multiple treatment options for patients with HER2-positive MBC.…”