ctDNA Drop ≥50% by Cycle 3 Flags Long-Term Benefit from Atezolizumab Across Solid Tumors

Cell-free DNA (cfDNA) refers to fragments of DNA released into the bloodstream from dying cells, including circulating tumor DNA (ctDNA) from cancer cells. In the MyPathway pan-tumor cohort (phase II, n = 153; NCT02091141), serial cfDNA sequencing showed that patients whose circulating-tumor-DNA tumor fraction fell ≥50% by cycle 3 day 1 (“molecular response”) enjoyed markedly better outcomes on atezolizumab—median PFS 9.7 vs 1.5 mo (HR 0.27) and OS 21.1 vs 14.3 mo (HR 0.44); the prognostic value held even within stable-disease cases. Baseline blood-TMB (bTMB) tracked with tissue-TMB only when ctDNA fraction ≥ 1%, emphasizing the importance for monitoring ctDNA levels to correlate bTMB to tissue-TMB.