Impact of detecting plasma EGFR mutations with ultrasensitive liquid biopsy in outcomes of NSCLC patients treated with first- or second-generation EGFR-TKIs

Abstract

BACKGROUND: Few trials have evaluated the utility of liquid biopsies to detect epidermal growth factor receptor mutations (EGFRm) at the time of response evaluation and its association with the clinical characteristics and outcomes of non-small-cell lung cancer (NSCLC) patients. OBJECTIVE: This study aimed to evaluate, in a real-world clinical setting, the prevalence of plasma EGFRm and its association with the clinical characteristics, response and survival outcomes of NSCLC patients under treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This observational study enrolled advanced or metastatic NSCLC patients, with confirmed tumor EGFRm, receiving treatment with first- or second-generation EGFR-TKIs. Blood samples for the detection of plasma EGFRm were collected at the time of response evaluation and processed using the Target Selector™ assay. The main outcomes were the detection rate of plasma EGFRm, median Progression-Free Survival (PFS) and Overall Survival (OS) according to plasma EGFR mutational status. RESULTS: Of 84 patients, 50 (59.5%) had an EGFRm detected in plasma. After a median follow-up of 21.1 months, 63 patients (75%) had disease progression. The detection rate of plasma EGFRm was significantly higher in patients with disease progression than in patients with partial response or stable disease (68.3% versus 33.3%; P< 0.01). PFS and OS were significantly longer in patients without plasma EGFRm than among patients with plasma EGFRm (14.3 months [95% CI, 9.25–19.39] vs 11.0 months [95% CI, 8.61–13.46]; P= 0.034) and (67.8 months [95% CI, 39.80–95.94] vs 32.0 months [95% CI, 17.12–46.93]; P= 0.006), respectively. A positive finding in LB was associated with the presence of ⩾ 3 more metastatic sites (P= 0.028), elevated serum carcinoembryonic (CEA) at disease progression (P= 0.015), and an increase in CEA with respect to baseline levels (P= 0.038). CONCLUSIONS: In NSCLC patients receiving EGFR-TKIs, the detection of plasma EGFRm at the time of tumor response evaluation is associated with poor clinical outcomes.

Efficacy of epidermal growth factor receptor tyrosine kinase inhibitor in the treatment of patients with nonsmall cell lung cancer

“…Several clinical studies have confirmed the effectiveness of EGFR-TKI-targeted therapy for the treatment of NSCLC, and its overall safety is good. [26][27][28][29][30][31] The effectiveness and safety of NSCLC patients with NSCLC have been studied, and the results showed that the objective remission rate of gefitinib in Chinese patients was 27%, DCR was 54%, and 1-year cumulative survival was 44%. [32] The results of this study are consistent with those of previous studies.…”