(a-b) Somatic mutations (SNV or Indel) (blue) of known or predicted functional significance (Methods) and copy-number gains (red), or both (pink) detected in patients who responded, n = 37 (a) or did not respond, n = 36 (b) to subsequent EGFR TKI treatment (see Online Methods). (c) Forest plot demonstrating effect of cfDNA detectable gene level alterations on EGFR TKI PFS determined by Cox-proportional Hazard Ratio (HR) with 95% CI. (d) Kaplan-Meier curves demonstrating difference in median PFS to EGFR TKI treatment (logrank test) in patients with cfDNA detectable alterations in CDK4 or CDK6. (e) Pathway level alterations detectable in cfDNA of patients who responded to subsequent EGFR TKI treatment (see methods) versus patients who did not respond (see methods). Q-values determined by two-tailed Fisher's Exact test with Benjamini-Hochbeg correction for multiple hypothesis testing. (f-h) Forest plot and Kaplan-Meier curves assessing the effects of indicated cfDNA detectable pathway alterations on PFS. See also Supplementary Data Sets 3 and 4.