An analysis of the genetic mutation of resistant advanced non-small cell lung cancer after treatment with the first generation of EGFR-TKIs

ObjectiveTo analyze the genetic mutation of resistant advanced non-small cell lung cancer (NSCLC) after treatment with the first generation of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and to investigate possible mechanisms of drug resistance. MethodsA total of 31 patients resistant to the first-generation of EGFR-TKIs were enrolled. Their mutational profiling was determined in a cohort using targeted next generation sequencing (NGS) of 123 cancer-related genes. The mutation of EGFR genes and other tumor related genes were analyzed, and the correlations between genetic mutation and clinical characteristics were analyzed. ResultsA total of 121 genetic mutations were found in 31 patients, with an average of 3.9 mutations per patient. There were 28 patients with EGFR sensitive mutations, including exon 19 mutation in 15 patients (48.4%). There were 14 patients with T790M mutations, including exon 21 mutation in 12 patients (38.7%). Meanwhile, there were 7 patients with mutation in both exons 19 and 20 (22.6%), and 5 patients in both exons 20 and 21 (16.1%). The rate of T790M mutation was 62.5% (10/16) for patients without tumor family history, which was significantly higher than that of those with tumor family history 26.7% (4/15) (P<0.05). The PIK3CA mutation rate was 21.4% (3/14) for female patients, which was significantly higher than that of male patients (0) (P<0.05). The PFS of T790M positive mutation patients was 12.6 months, compared with 7.8 months of negative patients, without statistical difference (P>0.05). The PFS of exon 21 L858R mutation positive patients was 14.4 months, which was statistical different from 7.4 months of negative patients (P<0.05). The PFS PIK3CA mutation positive patients was 3.0 months, which was statistical different from 10.9 months of negative patients (P<0.05). ConclusionsAccording to the mutational profiles of NSCLC patients resistant to the first-generation of EGFR-TKIs, individualized therapy can be determined. L858R and PIK3CA are related with the prognosis.