Les nouvelles thérapeutiques biologiques du cancer bronchique☆

Abstract

Therapies targeted on cell signal pathways that control cell division and tumor angiogenesis have been developed over the last five years for non small cell lung cancer (NSCLC) with some amazing results, in subgroups of selected patients, predicting more significant success in the upcoming years. Compounds targeted on EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3 trials including thousands of patients. Their efficacy has been proved, in second and third line trials, after first line cisplatin-based chemotherapy for non-mucinous adenocarcinoma in non-smokers, women and Asian patients. Response rates vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian patients with long survivals. Therapeutic targeting improves success rates, either relying on EGFR gene amplification detection by FISH, or search for EGFR tyrosine kinase domain mutations. Commercial kits are available for routine molecular diagnosis of domain mutations potentially enabling molecular targeting in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal antibody to VEGF, bevacizumab, have also been developed in the last few years. Bevacizumab associated with classical cytotoxic chemotherapy led, in selected patients (with non squamous cell lung cancer and no past history of cardiovascular disease) to an increase of median survival to more than 12 months with tolerable toxicity. Other drugs that have both anti-EGFR activity and anti-angiogenic properties will be soon developed, since future bioactive anti-cancer drugs will probably be multi-targeted drugs.