Les cancers bronchiques non à petites cellules EGFR-mutés

Since the discovery of Epidermal Growth Factor Receptor mutations in 2004, the treatment of EGFR-mutated non small cell lung cancers (NSCLC) has rapidly moved away from that of other NSCLC. EGFR-mutated NSCLC are characterized by a different carcinogenesis compared to tobacco-related cancers and a different epidemiology, with an increased frequency of EGFR mutations in never smokers, women, Asians and adenocarcinoma. Treatment of EGFR-mutated NSCLC relies on tyrosine kinase inhibitors (TKI) that demonstrated superiority over chemotherapy. In France, 3 TKI are available as first-line therapy including gefitinib, erlotinib and afatinib. The toxicity profile of these TKI is good, with skin rash and diarrhea being the most frequent adverse events. Therapeutic strategy in case of progression on EGFR TKI depends on the detection of a T790M resistance mutation, which can be found either in tumor tissue or liquid biopsies. Third-generation TKI such as osimertinib have shown activity in T790M positive NSCLC. Local treatments may also be proposed in case of local progression. Several questions remain unanswered, regarding treatment of NSCLC with rare EGFR mutations, optimal sequence for third-generation TKI and innovative combinations. This review will address all these aspects of EGFR-mutated NSCLC.