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.

Keywords:

• human epidermal growth factor receptor 2
• breast neoplasms
• central nervous system metastases
• trastuzumab

Disclosure

Dr Kakkar reports no conflicts of interest in this work. Dr Hurvitz received reimbursement for travel from Roche to present at an international symposium and has received research grant funding from Roche and GlaxoSmithKline.