Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors

Ann Pharmacother. 2006 Feb;40(2):261-9. doi: 10.1345/aph.1G387. Epub 2006 Jan 17.


Objective: To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and drug interactions of lapatinib.

Data sources: A PubMed search was conducted (1966-August 2005) using the following terms: lapatinib, GW572016, and dual tyrosine kinase inhibitor. Additional information sources included meeting abstracts, clinical trial data, and bibliographies from articles identified through PubMed.

Study selection and data extraction: Preclinical and clinical trials that evaluated lapatinib in cell culture, animal models, and human subjects were selected from the data sources. Pivotal in vitro data and all in vivo data published regarding lapatinib were included.

Data synthesis: The development of tyrosine kinase inhibitors has resulted from a search for targeted cancer therapeutics made possible by recent gains in our understanding of tumor cell biology. Lapatinib is a dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor and human epidermal growth factor receptor-2 autophosphorylation, leading to suppression of proliferation pathways of solid tumors. Lapatinib has shown clinical activity in solid tumors, with the most notable in advanced or metastatic breast cancer, including tumors refractory to trastuzumab. It has a mild adverse effect profile, with the most common adverse events being diarrhea and rash.

Conclusions: Lapatinib has novel, dual tyrosine kinase inhibitory properties selective for factors overexpressed in some solid tumors. Results from preclinical and Phase I/II trials indicate activity in the treatment of solid tumors, especially advanced or metastatic breast cancer. Application for approval is anticipated pending results of ongoing Phase III trials.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / therapeutic use
  • Clinical Trials as Topic
  • Drug Design
  • Humans
  • Lapatinib
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / pharmacokinetics
  • Protein Kinase Inhibitors* / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • PubMed
  • Quinazolines* / adverse effects
  • Quinazolines* / pharmacokinetics
  • Quinazolines* / therapeutic use


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Lapatinib
  • Protein-Tyrosine Kinases