Patients presenting with non-small cell lung cancer (NSCLC) and active EGFR 
mutation have a high response rate (60-70%) to EGFR tyrosine kinase inhibitors 
(TKI) with little immediate progression (primary resistance). However, 
progression on this treatment (secondary resistance) is inevitable even for 
those who responded initially. These two situations are distinct in terms of 
management. In case of primary resistance, screening for other associated 
molecular abnormalities (tumour heterogeneity) should be done, even resulting in 
a false positive in the initial screening of EGFR mutation. In case of secondary 
resistance, a new pathology sample should be taken insofar as is possible to 
determine the presence of an acquired mutation of EGFR resistance (T790M in 60% 
of cases) or c-Met amplification (20% of cases). The presence of a T790M 
mutation could respond to irreversible EGFR-TKI, while a c-Met amplification 
could be managed with a targeted anti-Met therapy. However, the gold standard is 
still cytotoxic chemotherapy at present if a clinical trial based on a targeted 
therapy is not possible.