Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA

SIMPLE SUMMARY: An early assessment of response to treatment is crucial to informing appropriate therapeutic management. Using a plasma-only strategy, we measured changes in circulating tumor DNA (ctDNA) levels after one or two cycles of chemotherapy in 92 patients with advanced non-small-cell lung cancer (NSCLC) treated with first-line chemo- or chemoradiation therapies. A ≤50% decrease in ctDNA level after one cycle of chemotherapy was associated with shorter progression-free survival and overall survival. A ≤50% decrease in ctDNA level after two cycles of chemotherapy also had shorter survival. Our findings demonstrate that using liquid biopsies to measure early changes in ctDNA levels in response to chemotherapy may help identify non-responders before standard-of-care imaging in advanced NSCLC. Monitoring treatment efficacy earlier and accurately can enable more personalized regimens to improve patient outcomes. ABSTRACT: Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. Plasma samples were collected from 92 patients with Stage IIIB-IV NSCLC treated with first-line chemo- or chemoradiation therapies in an observational, prospective study. Retrospective ctDNA analysis was performed using next-generation sequencing with a targeted 198-kb panel designed for lung cancer surveillance and monitoring. We assessed whether changes in ctDNA levels after one or two cycles of treatment were associated with clinical outcomes. Subjects with ≤50% decrease in ctDNA level after one cycle of chemotherapy had a lower 6-month progression-free survival rate (33% vs. 58%, HR 2.3, 95% CI 1.2 to 4.2, log-rank p = 0.009) and a lower 12-month overall survival rate (25% vs. 70%, HR 4.3, 95% CI 2.2 to 9.7, log-rank p < 0.001). Subjects with ≤50% decrease in ctDNA level after two cycles of chemotherapy also had shorter survival. Using non-invasive liquid biopsies to measure early changes in ctDNA levels in response to chemotherapy may help identify non-responders before standard-of-care imaging in advanced NSCLC.