Epidermal growth factor receptor inhibition in lung cancer: Status 2012

Fred R. Hirsch, Pasi A. Jänne, Wilfried E. Eberhardt, Federico Cappuzzo, Nick Thatcher, Robert Pirker, Hak Choy, Edward S. Kim, Luis Paz-Ares, David R Gandara, Yi Long Wu, Myung Ju Ahn, Tetsuya Mitsudomi, Frances A. Shepherd, Tony S. Mok

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing.

Original languageEnglish (US)
Pages (from-to)373-384
Number of pages12
JournalJournal of Thoracic Oncology
Volume8
Issue number3
DOIs
StatePublished - Mar 2013

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Keywords

  • Carcinoma
  • EGFR antibodies
  • Epidermal growth factor receptor
  • Molecular targeted therapy
  • Non-small-cell lung
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Hirsch, F. R., Jänne, P. A., Eberhardt, W. E., Cappuzzo, F., Thatcher, N., Pirker, R., Choy, H., Kim, E. S., Paz-Ares, L., Gandara, D. R., Wu, Y. L., Ahn, M. J., Mitsudomi, T., Shepherd, F. A., & Mok, T. S. (2013). Epidermal growth factor receptor inhibition in lung cancer: Status 2012. Journal of Thoracic Oncology, 8(3), 373-384. https://doi.org/10.1097/JTO.0b013e31827ed0ff