PMC8992510_01
PMC8992510_02
Kinetics of emergence of the C797S (G>C) somatic mutant variant during osimertinib treatment cycle. Results are shown as %MVF. For timepoints 0 and 42 C797S was ND. Although results were obtained for del19 and T790M for the day-164 specimen, the remaining specimen QNS for C797S testing at this time point. ND: not detected; QNS: quantity was not sufficient; %MVF: percent minor variant frequency
cdr-2-912.fig.1.jpg
PMC8992510_02_cdr-2-912.fig.1.jpg
fig1
The C797S mutation was undetectable on treatment days 0 and 42 but was detectable by day 287 [Figure 1].
Evolution of EGFR del19, T790M, and C797S during the 540-day osimertinib treatment cycle. Data are displayed as relative fluorescence units, and the calculated %MVF values are shown for each test. A and B: Del19 on days 0 and 540, respectively; C and D: T790M on days 0 and 540, respectively; E and F: C797S on days 0 and 540, respectively. EGFR L858R was consistently found to be negative by both ddPCR and NGS tests (data not shown). EGFR: epidermal growth factor; %MVF: percent minor variant frequency; ddPCR: droplet digital PCR; NGS: next-generation sequencing
cdr-2-912.fig.2.jpg
PMC8992510_02_cdr-2-912.fig.2.jpg
fig2
The EGFR del19 and T790M mutations both declined after initial osimertinib treatment but re-emerged by day 287 [Figures 2 and 3].
Detection of del19 driver and T790M TKI resistance mutations compared to C797S osimertinib resistance mutation (%MVF) over 540-day osimertinib treatment cycle. Note the day-164 specimen was unavailable for testing for C797S because the sample was exhausted. Insets: patient PET-CT scan on days 385 and 540 (showing disease progression). EGFR: epidermal growth factor; %MVF: percent minor variant frequency; TKI: tyrosine kinase inhibitor
cdr-2-912.fig.3.jpg
PMC8992510_02_cdr-2-912.fig.3.jpg
fig3
The EGFR del19 and T790M mutations both declined after initial osimertinib treatment but re-emerged by day 287 [Figures 2 and 3].