3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients

Background

Although liquid biopsy has been reported in detecting actionable mutations, and is becoming standard of care in non-small cell lung cancer (NSCLC) under certain circumstances, the relationship between plasma mutant allele fractions (MAFs) and treatment responsiveness remains unclear.

Methods

This study enrolled 134 patients with advanced NSCLC. Tumor tissue specimens were collected after surgery, and peripheral blood samples were collected at baseline (before surgery) and during treatments. Amplification-refractory mutation system (ARMS) was performed for EGFR mutation screening in all tumor tissues. Circulating single-molecule amplification and resequencing technology (cSMART) was performed in all cfDNA samples using a panel of nine genes including EGFR. EGFR status were compared between tumor tissue and matched cfDNA samples. Moreover, the association between MAFs of EGFR mutations in cfDNA and the responsiveness to tyrosine-kinase inhibitor (TKI) treatment was analyzed.

Results

EGFR mutations were detected in 56 tumor samples (56/134, ∼41.8%) and 67 matched baseline plasma cfDNA samples (67/134, 50.0%), the concordance rate between tumor and cfDNA samples is 82.8%. Specifically, EGFR exon19 non-frameshift deletions were detected in 24 tumor tissue and 23 matched cfDNA samples (concordance rate 97.8%), EGFR p.L858R mutations were detected in 24 tumor tissue and 22 matched cfDNA samples (concordance rate 97.0%). The overall response rate (ORR) and disease control rate (DCR) for EGFR mutation positive patients (TKI sensitive mutations only) were 47.6% and 73.8%, respectively. More importantly, for TKI-treated patients with original plasma EGFR MAFs higher than 0.1% and lower than 0.1%, the ORRs were 58.6% and 23.1% (17/29 versus 3/13 patients, P = 0.047), respectively.

Conclusions

In this study we confirmed that liquid biopsy based screening is reliable for actionable somatic mutation detection. The plasma mutant allele fraction of EGFR driver mutation tend to associate with the responsiveness to TKI targeted treatment. Larger cohorts are needed to clarify the impact of plasma MAFs in predicting treatment responsiveness.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.