Lapatinib in breast cancer.

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Aberrant activation of human epidermal growth factor receptor (HER) family members is crucial in breast cancer development.
• Lapatinib is an oral dual tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2.

Purpose of the Study:

• To evaluate the clinical efficacy and tolerability of lapatinib in various breast cancer settings.
• To explore lapatinib's potential in advanced, metastatic, and HER2-positive breast cancer, including cases with brain metastases and trastuzumab resistance.

Main Methods:

• Review of Phase I, II, and III clinical trial data for lapatinib in breast cancer patients.
• Analysis of interim results from a large Phase III trial comparing lapatinib plus capecitabine versus capecitabine alone.

Main Results:

• Lapatinib demonstrates activity as monotherapy and in combination, particularly in HER2-positive and trastuzumab-resistant breast cancer.
• Phase I trials show good tolerability with mild side effects and low cardiotoxicity.
• Interim Phase III results indicate that lapatinib combined with capecitabine significantly improves time to progression compared to capecitabine alone.

Conclusions:

• Lapatinib is a well-tolerated and effective targeted therapy for advanced or metastatic HER2-positive breast cancer.
• Ongoing trials are investigating lapatinib in combination with various agents and in different treatment settings (neoadjuvant/adjuvant).
• Advances in understanding breast cancer biology and biomarker use facilitate the clinical application of targeted therapies like lapatinib.