Table 1.
Biopsy Data, Treatment History of EGFR TKIs, and Representative Genetic Alterations From Individual Cases
| Case | EGFR TKI(s) Used Before Osimertinib |
Osimertinib Duration (m) | Tissue Biopsy |
OCA Ver. | Representative Genetic Alterations at Rebiopsy (Tissue) |
ccf DNA (Plasma) | Representative Genetic Alterations at Rebiopsy (Plasma) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EGFR TKI(s) | Duration (m) | Baseline | Rebiopsy | EGFR Common | T790M | C797S, etc. | SNV | CN Gain | EGFR Common | T790M | C797S, etc. | SNV | CN Gain | ||||
| 1 | A | 15.4 | 11.6 | DR | DR | 1 | Del19 | + | C797Sa | D | Del19 | + | C797S | KEAP1 | EGFR, MET | ||
| 2 | G, E | 27.1 | 11.1 | DR | DR | 1 | Del19 | + | C797S | NF1, GATA3 | EGFR | D | Del19 | + | C797S | KRAS | EGFR, MET |
| 3 | A | 20.6 | 12.6 | DR | DR | 1 | Del19 | + | C797S | EGFR | D | Del19 | + | C797S | ERBB2 | EGFR, MET | |
| 4 | G | 46 | 28.6 | DR | DR | 1 | L858R | + | C797S | EGFR | D | L858R | + | C797S | EGFR | ||
| 5 | A | 40.7 | 29.1 | DR | DR | 3 | Del19 | + | C797S | MYCN | D | Del19 | |||||
| 6 | G, BE | 18.9 | 17.6 | DR | DR | 1 | L858R | + | G796S | D | L858R | ||||||
| 7 | G | 31.6 | 19.8 | DR | DR | 1 | L858R | + | C797S | CDK6 | NA | ||||||
| 8 | G | 24.2 | 13.4 | D | DR | 1 | L858R | EGFR, MET, CDK4 | D | L858R | EGFR, MET | ||||||
| 9 | G | 24.4 | 8.8 | D | DR | 3 | ND | BRAF, IDH2 | D | ND | + | ||||||
| 10 | G, E, A | 25.3 | 19.4 | DR | DR | 3 | Del19 | CDK4b | D | Del19 | |||||||
| 11 | G, BE | 24.7 | 18.5 | DR | DR | 1 | L858R | NA | |||||||||
| 12 | G, E, A, E, A | 25.2 | 12.6 | DR | DR | 1 | L858R | ATM | GAS6 | D | L858R | EGFR | |||||
| 13 | G, A | 18.6 | 19.8 | X | DR | 3 | Del19 | + | C797Sc | PTENd | D | Del19 | + | C797S | EGFR, MET | ||
| 14 | G | 7.6 | 22.9 | X | D | 1 | Del19 | + | C797S | CTNNB1, SMAD4d | D | Del19 | + | C797S | |||
| 15 | G, E | 19.4 | 24.3 | X | DR | 3 | L858R | + | L792V | EGFR, CDK4d | D | L858R | + | L792V | EGFR | ||
| 16 | G | 11.7 | 17 | R | DR | 3 | Del19 | + | C797S | CDKN2A, IDH2d | NA | ||||||
| 17 | S | 27.9 | 18.2 | X | DR | 3 | Del19 | + | D | Del19 | + | EGFR, MET | |||||
| 18 | E, INV | 26.1 | 23.7 | X | DR | 1 | Del19 | + | PIK3CAd | D | Del19 | + | ERBB2 | ||||
| 19 | E | 35.4 | 19.1 | X | DR | 1 | Del19 | PIK3CAd | CDK4, CCND1d | D | Del19 | ||||||
| 20 | G | 33.1 | 23.1 | R | R | 1 | NA | ||||||||||
A, afatinib; BE, bevacizumab + erlotinib; ccfDNA, circulating cell-free DNA; CN, copy number; D, DNA; Del19, exon 19 deletion; DR, DNA and RNA; E, erlotinib; G, gefitinib; INV, investigational agent; NA, not available; ND, not detected; OCA, Oncomine Comprehensive Assay; R: RNA; SNV, single nucleotide variant; Ver., version; X: no data.
Cis/trans to T790M.
Also detected in baseline data.
Trans to T790M.
Possible mechanism, baseline data not available.