Table 3.

Observed mechanisms of resistance by tissue and ctDNA NGS in pretherapy, on-therapy, and posttherapy samples

Patient numberBaselineAcquired
1EGFR amp heterogeneity (only in metastasis, not in primary tumor), MYC ampMYC amp, PTEN deletion tissue, PIK3CA ctDNA
2EGFR/HER2 coamp primary tumor: 50% HER2 amp, other 50% EGFR amp; EGFR/MYC amp in ctDNAResidual HER2 amp and now-absent EGFR amp in residual primary tumor; KRAS amp clone in ctDNA
3None identifiedAbsent EGFR amp in residual primary tumor and recurrent lung metastases. New BRAF/MET/MYC amp in ctDNA
4K-NRAS/HER2/MYC/CCNE1/CCND1 coamp in primary tumor and ctDNAIncrease in NRAS/HER2/MYC amp and de novo GNAS-mutated clone in ctDNA
5MET/EGFR coamp in tumor and ctDNA, but KRAS-mutated liver biopsy but no EGFR ampIncreasing KRAS-mutated ctDNA, absent EGFR amp in tissue and ctDNA
6KRAS/MYC/CCNE1 amp and GNAS-mutated clone in ctDNAKRAS/MYC/CCNE1 amp and GNAS-mutated clone in ctDNA
7EGFR-amp heterogeneity (only in 10% of primary tumor, not metastasis or ctDNA)None yet identified
8EGFR/MET/HER2 coamp in primary tumor (different clones by FISH)Never treated