The Mechanism Of Acquired Drug Resistance After EGFR-TKI Treatment Of Non-small Cell Lung Cancer

BackgroundEpidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)sensitive non-small cell lung cancer(NSCLC)usually responds well to TKI treatment.However,most patients still develop into progressive disease in 12 months,suggesting that there are mechanisms of acquired resistance to EGFR-TKI.To overcome the resistance and bring patients more effective treatment,it is very important to find out the exact mechanisms.Methods25 Patients treated in Peking Union Medical College Hospital from 2010 to 2017.5,who developed acquired resistance to first generation EGFR-TKIs and underwent post-progression biopsies were enrolled.A total of 416 genes were sequenced and analyzed together with clinical data.ResultsWe identified EGFR T790M mutation from 12/25 patients(48%),and PIK3CA mutation from 3/25 patients(12%),2 of which also bear T790M mutation.MET amplification was identified in 2/25 patients(80%)and both with T790M.Other potential mechanisms leading to the acquired resistance are noted.We also find that T790M mutation tend to be positive in aged patients,like in patients over 60(83.3%),while patients younger than 60 seem to have a quite low chance to be identified with T790M mutation(15.4%).No other factors were considered to be statistically significant.ConclusionEGFR T790M may be the most common mechanism of acquired resistance to EGFR-TKI.Patients over 60 years old are more likely to acquire T790M mutation.Some other gene variations like EGFR L833F,FGFR1 amplification,AKT2 amplification,PTEN deletion may also be mechanisms of acquired resistance to EGFR-TKI.