Plasma-based next generation sequencing in advanced non-small cell lung cancer (NSCLC): significance in diagnosis and treatment in Asian patients.

NGS is recommended by NCCN and ESMO in evaluation of advanced NSCLC prior to treatment as being eligible for target therapy has important treatment implications. However, up to 20% of tissue biopsies are insufficient to run molecular testing for all nine FDA approved biomarkers. Currently, major guidelines recommend in the metastatic treatment naïve setting to pursue first line plasma-based NGS only if there is insufficient tissue. In our retrospective cohort, it was found that in 43 patients who underwent first line plasma-based and tissue NGS, 22 were Asians. Eleven of the twenty-two (50%) patients had an actionable mutation. The overwhelming majority of those mutations were EGFR actionable mutation (81.8%). All EGFR actionable mutations found on tissue was seen on plasma-based NGS, but 2 EGFR actionable mutation were seen on plasma-based NGS only. 22.2% of EGFR actionable mutations would have been missed if tissue-based NGS was pursued alone in the first line. In addition, in both plasma-based and tissue NGS, there is a statistically significant higher chance of detecting an EGFR actionable mutation if you were Asian compared to White (P = 0.004) or a nonsmoker compared to a smoker (P = 0.017). A small number of patients were found to have an EGFR actionable mutation on plasma-based NGS but not tissue NGS despite sufficient tissue to run NGS. They derived varying degrees of benefit from targeted therapy. Based on these findings patients who are Asian or nonsmoker plasma-based NGS should be considered in the diagnostic setting even if there is sufficient tissue for NGS.