Real‐world analysis of the prognostic value of EGFR mutation detection in plasma ctDNA from patients with advanced non‐small cell lung cancer

Abstract Background The plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non‐small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in baseline plasma ctDNA of advanced NSCLC can predict prognosis in addition to guiding targeted therapy remains to be further explored. Material and Methods In total, 315 NSCLC patients were retrospectively enrolled. EGFR mutation data from tissue detected by ARMS‐PCR and paired plasma samples within 1 month of admission detected by SuperARMS or ARMS‐PCR were collected. The correlation between baseline plasma ctDNA EGFR mutation status and survival was compared. Results EGFR mutation detection rates in tumor samples and plasma samples were 65.1% (205/315) and 43.8% (138/315). Referred to tissue results, the consistent rate of test ctDNA EGFR alteration by SuperARMS was higher than that detected by ARMS (79.5% vs. 69.0%, p = 0.04), either in stage I–IIIA patients (85.7% vs. 50.0%, p = 0.4) or stage IIIB–IV patients (79.1% vs. 69.4%, p = 0.04). Patients' treatment status and pathological subtype were the two factors that affected plasma ctDNA EGFR alteration detection accuracy. The concordance in non‐adenocarcinoma patients was obviously higher than that in adenocarcinoma (p = 0.02), and the concordance in treatment naïve patients was significantly higher than that in relapse patients (p = 0.047). In treatment naïve patients, the median PFS (mPFS) in plasma ctDNA EGFR‐positive patients was shorter than that in plasma ctDNA EGFR negative patients (7.0 vs. 10.0 months, p = 0.01). In relapsed patients, the mPFS in plasma ctDNA EGFR‐positive patients was 9.0 months versus 11.0 months in plasma ctDNA EGFR negative patients (p = 0.1). Conclusions A plasma sample could be an alternative for a molecular test when tissue samples was unavailable. The SuperARMS‐PCR detection method has high sensitivity in real‐world clinical practice. Furthermore, in patients with stage IIIB‐IV, baseline plasma ctDNA EGFR mutation positivity not only guides targeted therapy but also predicts a worse prognosis.