ABSTRACT
The aim of our trial was to evaluate the prognostic significance of qualitative ctDNA analysis on different stages of EGFR mutated non-small cell lung cancer (NSCLC) treatment. We included 99 patients amendable for the first line treatment with either gefitinib/erlotinib (n = 87), afatinib (n = 10) or osimertinib (n = 2). Sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 were performed before first dose, after 2 and 4 months of treatment, and on progression. Our analysis showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line tyrosine kinase inhibitors (TKIs) in terms of progression-free and overall survival. When treated with conventional approach, i.e. monotherapy with TKIs, the patients falls into three subgroups based on ctDNA analysis before and after 2 months of treatment. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 - 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 - 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcome of patients.
