Prognostic significance of longitudinal evaluation on egfr mutant ctdna during tki treatment in nsclc

Detection of EGFR mutations in tumor tissue is the gold standard for prescribing tyrosine kinase inhibitor therapy.However even in the same molecularly defined population effect of the treatment, response duration and survival might differ significantly. We did a prospective clinical trial to assess ctDNA-based EGFR mutations as a prognostic marker for patients with lung adenocarcinoma receiving TKI as first-line treatment.

Materials and methods. A total of 122 patients with lung adenocarcinoma had EGFR mutations in tumor tissue. The determination of ctDNA was performed before the start of therapy. The determination of ctDNA after 2 months of the therapy was performed for 99 patients.

Results. In 32/99 samples taken before the start of TKI therapy and after 2 months of therapy, no ctDNA was detected(group 1). In 67/99 patients, ctDNA was detected before the start of drug therapy: in 42/67 (62,7%) ctDNA was not detected in blood after 2 months of therapy (group 2), in 25/67 (37,3%) patient ctDNA was detected in blood during therapy (group 3). Survival was significantly higher in the group with no ctDNA compared to the group where the ctDNA was determined before starting therapy (56,2 months vs 15,4 months, p<0,000).
The objective response was significantly higher in the 1st and 2nd groups compared to the 3rd group (50% and 66,7%
vs 28,0%, p=0,002). PFS was also higher in groups 1 and 2 compared to groups 3 (24,1 months and 19,0 months vs 10,3
months, p=0,003).

Conclusions. The absence of EGFR mutated ctDNA at baseline and clearance after 2 months of TKI therapy defines a
group with the best prognosis.