Abstract:

Objective

To investigate the prognostic value of plasma circulating tumor DNA （EGFR）in epidermal growth factor receptor （EGFR）-tyrosine kinase inhibitors （TKIs） in patients with advanced nonsmall cell lung cancer （NSCLC）.

Methods

This study reviewed 127 patients with mutant advanced NSCLC who underwent EGFR gene testing in our hospital between January 2016 and June 2022. EGFR mutation was detected by direct sequencing method and divided into four groups according to mutation sites： exon （E） 18 mutant group， E19 mutant group， E20 mutant group， and E21 mutant group. In addition， E19 deletion mutations were divided into three subtype groups based on mutation patterns： codon deletion （CD）， codon substitution and skipping （CSS）， and CD or CSS plus single nucleotide variant （SNV） （CD/CSS+SNV）. The main outcome measures were progression-free survival （PFS） and overall survival （OS）.

Results

Among EGFR mutations， E19 deletion was the most common73cases （57.48%）， followed by E21 mutation 40cases（31.50%）， E18 mutation 6cases（4.72%）， and E20 mutation 8 cases （6.30%）. The median follow-up time for all NSCLC patients was 22.23 months （range 3.02 to 60 months）. Patients with E19 mutation had the longest median PFS and OS duration （13 months，30.59 months）， and were significantly longer than those with E18 mutation （9 months， 10.85 months）， E20 mutation （10 months， 19.48 months）， and E21 mutation （10 months， 16.92 months） （P＜0.05）. In the multivariate analysis model， E19 mutation was an independent influencing factor for PFS and OS in NSCLC patients （P＜0.05）. Among patients with E19 mutations， the median PFS and median OS （43 months， 51.25 months） in the CD/CSS+SNV group were significantly longer than those in the CD group （12 months， 29.87 months） and CSS group （10 months， 20.66 months） （P＜0.05）. The number of missing bases and missing amino acids in CD/CSS+SNV group （12.80±2.88， 4.40±0.91） were significantly lower than those in CD group （14.87±0.88， 4.98±0.33） and CSS group （16.73±3.35， 5.81±0.98） （P＜0.05）.

Conclusion

Compared with patients with E18/20/21 mutations， patients with E19 deletion mutations have a better prognosis for PFS and OS， suggesting that E19 deletion is a predictor of a better prognosis for PFS and OS in patients with EGFR mutant NSCLC. In addition， CD/CSS SNV was significantly associated with longer PFS and OS in patients with E19 mutations.

Key words: Non-small cell lung cancer, Epidermal growth factor receptor mutant subtype, Exon 19 deletion mutation, Prognosis