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.
- Yaung, S. J.
- Woestmann, C.
- Ju, C.
- Ma, X. M.
- Gattam, S.
- Zhou, Y.
- Xi, L.
- Pal, S.
- Balasubramanyam, A.
- Tikoo, N.
- Heussel, C. P.
- Thomas, M.
- Kriegsmann, M.
- Meister, M.
- Schneider, M. A.
- Herth, F. J.
- Wehnl, B.
- Diehn, M.
- Alizadeh, A. A.
- Palma, J. F.
- Muley, T.
Keywords
- Ngs
- Nsclc
- chemotherapy
- ctDNA
- early molecular response
