Early Assessment Of Therapy Response In Non-Small Cell Lung Cancer (Nsclc) Via Longitudinal Ctdna Analysis.

8577 Background: From the prospective, observational German Lung Cancer Multi-Marker Study we selected the first 72 consecutive small-cell lung cancer (SCLC) patients, UICC-stage IIIB/IV, where plasma samples were available prior to start of therapy, and prior to the second cycle of chemotherapy, and prior to third cycle. We hypothesized that assessment of the level of ctDNA after starting therapy relates to treatment effect and prognosis. Methods: We employed AVENIO ctDNA Surveillance Kit, a 197-gene NGS assay, which allowed us to perform longitudinal ctDNA analysis and measure the mutant molecules per milliliter-of-plasma (MMPM), which quantifies ctDNA over all variants of all sequenced genomic regions. All extracted cfDNA samples were processed and sequenced in order of date of blood draw. Results: At baseline (b0), we identified variants in all (72/72) subjects to enable ctDNA monitoring. Using serial liquid biopsies from each subject, the mean MMPM at post-first treatment cycle (p1) and the mean MMPM at post-second treatment cycle (p2) were analyzed. We tested a Continuous Responder algorithm, defined by a continuous drop in ctDNA levels represented by mean MMPM reduction over time (p2 < p1 < b0), to a mean MMPM below 20 at p2. As a result, continuous responders 26/72 were associated with a better therapy response OS HR = 1.9 (95% CI 1.1 – 3.2, log-rank P = 0.015). The continuous responders demonstrated a median survival benefit of 4.4 months over the poor responders. Neither gender, nor age, nor ECOG, nor stage were predictors of response in the models. Conclusions: An early assessment of treatment effect can be measured by mutant molecule counts in the plasma. A decrease in post-treatment ctDNA levels was associated with better prognosis in advanced SCLC.