Protein kinase inhibitors to treat non-small-cell lung cancer

Introduction:Activating mutations of the EGFRand rearrangement of anaplastic lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular characterization in NSCLC patients.Areas covered:For this review article, all published data on the most relevant Phase III trials with tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed.Expert opinion:Eight Phase III trials clearly established EGFR TKIs as the best therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated NSCLC, EGFR TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFRmutations, whereas in the EGFRwild-type population, a similar efficacy to docetaxel or pemetrexed in term of survival has been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the superiority of a multi-target TKI, including ALK, in terms of progression-free survival, response rate and toxicity profile when compared to standard second-line chemotherapy. New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.