Fig. 4: ctDNA dynamics and genomic alterations at disease progression. Source data are provided as source data file.
a Dynamics of EGFRm (copies/mL) between baseline and week 4 (n = 36), and baseline and week 12 (n = 34) in participants achieving PR, SD, and PD. Data are presented as median ctDNA copies/mL ± 95% confidence interval. Comparisons between baseline and week 4, and baseline and week 12 were made using a two-tailed Wilcoxon signed-rank test. All P values are exact. Each dot represents a single participant. b Kaplan-Meier estimate of OS for participants (n = 34) stratified according to EGFRm W12-BLR ≤median and >median. Comparisons were made using a two-sided log-rank test and no adjustments were made for multiple comparisons. c Kaplan-Meier estimate of OS for participants (n = 35) stratified according to T790M W12-BLR ≤median and >median. Comparisons were made using a two-sided log-rank test and no adjustments were made for multiple comparisons. d Kaplan-Meier estimate of OS for participants (n = 34) stratified according to clearance versus non-clearance of EGFRm DNA (copies/mL) by week 12. Comparisons were made using a two-sided log-rank test and no adjustments were made for multiple comparisons. e Kaplan-Meier estimate of OS for participants (n = 32) stratified according to clearance versus non-clearance of T790M mutant DNA (copies/mL) by week 12. Comparisons were made using a two-sided log-rank test and no adjustments were made for multiple comparisons. f Summary of ctDNA genomic features at disease progression in 27 and 21 participants who completed alternating therapy and proceeded with continuous osimertinib following progression on alternating therapy, respectively with an available progression plasma sample. Participants are ordered according to time to progression (indicated by grey shaded colored boxes) in the order of 0–6 months, 6–12 months, and >12 months. Each column represents an individual participant, and each row indicates a specific acquired alteration. The colour of bars is indicative of the type of mutation with grey = wild-type.*Participants 8 and 17 progressed on induction osimertinib and never proceeded to alternating therapy. EGFRm epidermal growth factor receptor mutation, PR partial response, SD, stable disease, PD progressive disease, W12-BLR, week 12 to baseline ratio, OS overall survival.
