Evaluating Circulating Tumor DNA Clearance as an Early Intermediate End Point Predicting Clinical Benefit in Metastatic Nonsquamous NSCLC After First-Line Chemoimmunotherapy

ctDNA decline is associated with improved survival outcomes in a clear dose-response manner. ctDNA clearance and radiologic response provide complementary prognostic information, and combining these end points (ctDNA_CL + Resp) can further improve prediction of PFS and OS. This combination also enhanced the correlation between treatment effects on the early end points and PFS/OS at the trial level. However, their overall ability to predict treatment effects at the trial level remained modest for both PFS and OS, likely due to the limited data from a single study. Further validation in larger, multi-trial data sets is needed to establish ctDNA clearance as a reliable early surrogate end point in first-line NSCLC.