Mutation burden of plasma circulating tumor DNA (ctDNA) was found to be substantially decreased after initial treatment of non-small cell lung cancer (NSCLC) but remained constant thereafter, according to the results of a study published in the Journal of Clinical Oncology Precision Oncology.1

Previous studies suggest that treatment efficacy and better clinical outcomes are associated with a reduction in plasma ctDNA variant levels. The aim of this study was to determine how anticancer treatment may influence plasma ctDNA.

The study included data from three phase 1 National Cancer Institute (NCI) trials of 38 patients with EGFR-mutant NSCLC treated with osimertinib and an institutional cohort of 79 patients with NSCLC harboring KRAS, EGFR, or BRAF alterations. An imaging cohort of 43 patients with advanced EGFR-mutant NSCLC was also included. Plasma was collected at baseline and before each treatment cycle. Droplet digital polymerase chain reaction was used to analyze ctDNA.

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The greatest change in plasma ctDNA mutation abundance occurred after the first treatment. In the NCI cohort, 87.5% of patients demonstrated a plasma response. Analysis of ctDNA at 20 to 28 days after treatment start demonstrated a 90% or greater decrease in mutation abundance among 87.5% of patients.

Among patients in the institutional cohort, 90.3% demonstrated a plasma response.  A 90% or greater decrease in mutation abundance occurred among 83.9% of patients at 7 to 30 days after their first treatment. Of the 62 evaluable patients, 35 demonstrated a complete plasma response, with 71.4% detected at the first follow-up evaluation.

The authors concluded that “plasma ctDNA response is an early phenomenon, and the optimal initial assessment may during or at the end of the first cycle of therapy, rather than in concert with standard imaging timepoints.”


Cheng ML, Lau CJ, Milan MSD, et al. Plasma ctDNA response is an early marker of treatment effect in advanced NSCLC. JCO Prec Oncol. 2021;5:393-401. doi:10.1200/PO.20.00419