[Management of patients with resistance to EGFR-TKI]

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.