Recent advances in the molecular characterization of metastatic unresectable lung cancers have markedly improved the management of patients. Today, molecular tests should be performed routinely in all patients with non-squamous non-small cell lung cancer, and in case of squamous cell carcinoma occurring in a non-smoker. In the presence of EGFR mutation or ALK rearrangement, specific inhibitors have shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib). We will report the most recent clinical trials that aimed to identify effective therapeutic alternatives in case of acquired resistance to first-generation inhibitors (erlotinib, gefitnib, crizotinib), which inevitably occur in a median of 11-13 months at the first line setting and 7 months at the second line setting. Finally, we will describe more recently known molecular alterations such as ROS1 or RET rearrangements and HER2, BRAF, PIK3CA, DDR2 mutations. Some of these alterations are already elegible for dedicated targeted therapies within clinical trials or temporary use authorization (ATU).
Keywords: Cancer bronchique non à petites cellules métastatiques non résécable; Drug resistance; Fusion de gènes; Gene fusion; Molecular targeted therapy; Mutation; Résistance aux traitements; Thérapies moléculaires ciblées; Unresectable metastatic non-small cell lung cancer.
Copyright © 2014. Published by Elsevier Masson SAS.