[Frontiers in Bioscience S3, 501-517, January 1, 2011]

EGFR pathway in advanced non-small cell lung cancer

Valentina Merlo1, Marina Longo2, Silvia Novello2, Giorgio Vittorio Scagliotti2

1Department of Medical Oncology, Santa Maria della Misericordia University Hospital, Udine, Italy, 2Thoracic Oncology Unit, University of Turin, AOU San Luig Gonzaga-Orbassano (TO), Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. EGFR
3. Erlotinib
3.1. First line therapy
3.2. Second-third line therapy
3.3. Maintenance therapy
4. Gefitinib
4.1. First line treatment
4.1.1. Single agents studies
4.1.2. First line studies in combination with chemotherapy
4.2. Second line studies
4.3. Maintenance therapy
5.Cetuximab
5.1. First line studies
5.2. Second line studies
6. Perspectives
7. References

1. ABSTRACT

Chemotherapy is the standard of care for patients with advanced stage non-small cell lung cancer (NSCLC) because of the a modest improvement in survival and quality of life but its efficacy has already reached a plateau. Several molecular targets involved in the uncontrolled growth of lung cancer cells has been recently discovered and Epidermal Growth Factor Receptor (EGFR) pathway is as a key therapeutic target. Strategies to block such pathway include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. Erlotinib and gefitinib are two EGFR-TKI active against NSCLC. Their efficacy has been proven to be definitively superior in presence of activating EGFR mutation in the tumor. This evidence does not apply to the monoclonal antibody cetuximab, which efficacy in NSCLC was recently demonstrated in a single phase III study. The good tolerability profile of EGFR inhibitors make these agents suitable for maintenance and adjuvant setting, while sequencing of EGFR-TKIs and chemotherapy seems to be preferred. This article reviews the role of EGFR inhibitors focusing mainly on compounds in phase III clinical development.