Epidermal growth factor receptor ( EGFR ) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study

Abstract

Introduction

Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients.

Methods

Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF). Amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) were used to identify the T790M mutation in ctDNA. Prognosis was analyzed with Kaplan–Meier methods.

Results

Overall concordance between the two methods was 78.3%. According to both ARMS and ddPCR, patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups (P < 0.001), and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups (P < 0.001). AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+ patients in all groups who had progressed on EGFR-TKIs; for other treatments, the prognosis of T790M− patient subgroups varied.

Conclusions

The present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influence treatment selection and prognosis.

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