Predictive significance of circulating tumor DNA against patients with T790M- positive EGFR-mutant NSCLC receiving osimertinib

Abstract Background: Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. Data regarding the predictive significance of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Thus, this study analyzed ctDNA during osimertinib administration as a second-line or greater setting to examine the association between EGFR mutation levels and clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC).Methods: Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were enrolled. Plasma samples were obtained at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed using digital polymerase chain reaction.Results: The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib treatment than at pretreatment and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. There was no statistically significant difference in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD.T790M detection at PD after osimertinib initiation was a significant independent prognostic factor for predicting worse prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely associated with shorter survival after osimertinib initiation.Conclusion: Molecular testing based on ctDNA is useful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.