Inhibitors of the EGFR pathway in non small cell lung cancer: what"s new in 2007?

Non small cell lung cancer (NSCLC) is a major health public issue because of its frequency and related mortality. Progress with chemotherapy in advanced NSCLC has reached a plateau and more effective and better tolerated therapeutic strategies are needed. Epidermal growth factor receptor (EGFR) is overexpressed in 80% of NSCLC and inhibitors of EGFR tyrosine kinase have now an important place in the management of NSCLC. Most significant results have been obtained with oral inhibitors like erlotinib or gefitinib. Erlotinib role in second and third line setting is firmly established. Recent data suggests that in the first line setting, interesting overall response rates improving survivals can be obtained. in specific subpopulations defined either by histology (adenocarcinomas, adenocarcinomas with bronchioloalveolar features), sex (women), non-smoking status (never-smokers) or biological markers (tumours with EGFR mutations in exons 18-21). Such improvements are especially valuable because inhibitors of EGFR tyrosine kinase are better tolerated than chemotherapy. The exact contribution of monoclonal antibodies like cetuximab is still unclear in NSCLC.