Treating acquired resistance to EGFR-tyrosine kinase inhibitors:still a work in progress.

While most patients with metastatic non-small cell lung cancer (NSCLC) containing sensitizing mutations in the epidermal growth factor receptor (EGFR) gene will achieve an objective response to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib or gefitinib, patients inevitably develop resistance to these agents. One of the strategies being tested to overcome acquired resistance to EGFR TKIs is the use of irreversible EGFR inhibitors such as afatinib. In the randomized phase 2b/3 LUX-Lung 1 trial in advanced NSCLC patients who progressed after at least 12 weeks of benefit from EGFR TKIs, afatinib failed to improve overall survival compared to placebo. Although the liberal entry criteria likely allowed the inclusion of some patients without true acquired resistance, the failure of this study calls into question the viability of irreversible EGFR inhibitors in this patient population.

RCT Entities:   Population Interventions Outcomes