Monitoring of EGFRm level in cfDNA in patients with advanced NSCLC on the gefitinib therapy

Background

The aims in this study were to evaluate level of EGFR mutations in plasma in advanced NSCLC on the treatment with TKIs in the 1^st and 2^nd lines, to compare mutation status in FFPE tissue and plasma samples and to evaluate diagnostic characteristics of real-time wild-type blocking PCR (LNA-clamp) assay and digital PCR (dPCR).

Methods

Analysis was carried out in 2 groups: in the 1^st group patients received gefitinib in the 1st line (n = 22), in the 2^nd group- in the 2nd line (n = 13). Detection of EGFR mutation in cfDNA was conducted prior to the target therapy and during this treatment in both groups. Some patients (n = 14) were enrolled 2-23 months after the start of therapy and EGFRm status prior to the gefitinib administration was not estimated. Plasma samples for detection of del19, L858R and T790M mutations were collected monthly prior to the next therapy cycle. EGFR mutation status was assessed using 2 methods - allele-specific PCR with the modifications (TaqMan-LNA, Real-time) and QuantStudio 3D Digital PCR.

Results

A month after the start of the gefitinib administration, the EGFR mutations status in plasma has become negative in all patients. Negative EGFR mutations status persisted until progression. In total, progression has occurred in 19 (54%) patients. In 7 (36,8%) of them it correlated with T790M mutation appearance, in 4 (21,1%)- with both T790M and activating EGFR mutation appearance, in 2 (10,5%)- with only activating mutation reappearance and in 6 (31,6%) patients EGFR mutation status persisted negative. The mean value of EGFR+ cfDNA prior the 1^st line of therapy was statistically higher than in progression and prior to the 2^nd line: 1,88% (95% CI: 1,14;2.62), 0,3% (95% CI: 0.04;0.56) p 

Conclusions

Change of EGFR mutation level in cfDNA can be used as a marker of efficacy of EGFR-TKIs therapy and as a progression predictor.

Clinical trial identification

Legal entity responsible for the study

Republican Clinical Oncology Center - Ufa, Kazan Clinical Oncology Center

Funding

Republican Clinical Oncology Center - Ufa, Kazan Clinical Oncology Center

Disclosure

All authors have declared no conflicts of interest.