The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare.
Weiting LiKlaas KokGeok Wee TanPei MengMirjam MastikNaomi RifaelaFrank ScherpenThijo Jeroen N HiltermannHarry J M GroenAnthonie J van der WekkenAnke Van den BergPublished in: Cancers (2022)
EGFR-mutated non-small cell lung cancer (NSCLC) patients can be effectively treated with tyrosine kinase inhibitors (TKI) but frequently present with an EGFR T790M resistance mutation at relapse. We aimed to screen for T790M in pre-treatment formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients with a confirmed T790M mutation at progression. We analyzed 33 pre-treatment DNA samples of NSCLC patients who progressed upon TKI between 2013 to 2019. To establish storage-time dependent formalin fixation-induced background levels for C>T mutations, we analyzed DNA isolated from archival (stored >1 year, n = 22) and recently generated (stored <1 month, n = 11) FFPE samples and included DNA isolated from white blood cells (WBC) ( n = 24) as controls. DNA samples were analyzed by droplet digital (dd)PCR, and positivity was defined by outlier detection according to Grubb's criterion. The T790M background allele frequency levels were 0.160% in DNA isolated from archival-FFPE, 0.100% in fresh FFPE, and 0.035% in WBC. Progression-free survival (PFS) time of the single T790M positive patient was 9 months, while T790M negative patients had a median PFS of 10 months (range 2-27). Proper storage time matched FFPE control samples are essential for reliable detection of T790M mutation at low VAF. The presence of EGFR T790M mutations in pre-TKI samples is rare, even in patients who progressed with EGFR T790M mutations.
Keyphrases
- tyrosine kinase
- small cell lung cancer
- epidermal growth factor receptor
- advanced non small cell lung cancer
- circulating tumor
- free survival
- end stage renal disease
- cell free
- single molecule
- newly diagnosed
- ejection fraction
- chronic myeloid leukemia
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- high throughput
- patient reported outcomes
- room temperature
- nucleic acid
- signaling pathway
- cell cycle arrest
- brain metastases
- patient reported
- real time pcr
- high glucose