Heterogeneity in resistance mechanisms causes shorter duration of epidermal growth factor receptor kinase inhibitor treatment in lung cancer

We observed heterogeneity of resistance mechanisms in two of four patients analyzed (T790M + MET gene copy number gain, and mutant EGFR loss + unknown). We also identified quantitative heterogeneity in EGFR T790M mutation ratio among EGFR-TKI refractory lesions. In analyzing patient outcomes, we found that patients who developed multiple resistance mechanisms had shorter TTF compared with those who developed single resistance mechanism (p = 0.022). PPS after EGFR-TKI treatment failure was compatible between these two groups (p = 0.42). These findings further our understanding of acquired resistance mechanisms to EGFR-TKIs, and may lead to better treatment strategies after acquisition of resistance to first generation EGFR-TKIs in lung cancer patients with EGFR mutations.