EGFR plasma mutation in prediction models for resistance with EGFR TKI and survival of non‐small cell lung cancer

Abstract

Background This study aims to clarify the prognostic role of epidermal growth factor receptor ( EGFR ) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. A total of 94 Adenocarcinoma, clinical stage IV NSCLC patients with either E19del or L858R mutation were admitted to the prospective study from Jan-2016 to Jul-2018. EGFR mutations in plasma were detected by scorpions ARMS method. The Kaplan–Meier and Cox regression methods were used to estimate and test the difference of progression-free survival (PFS) and overall survival (OS) between groups. The prognostic power of each factor was appraised by the Bayesian Model Averaging (BMA) method. Results Among 94 patients, 28 cases still are good responses according to the RECIST criteria and negative for EGFR mutations in plasma. Of 66 resistant patients, EGFR mutations were positive in plasma of 57 cases (86.4%) which was higher than the value of pre-treatment (48.5%). Of which, 17 patients (25.8%) have the occurrence of EGFR mutations in plasma earlier than progression 2.1 (0.6–7.9) months. The secondary T790M mutation was found in the plasma of 32 cases (48.5%). Median PFS and OS for the study subjects were 12.9 (11.0–14.2) and 29.5 (25.2–41.3) months, respectively. The post-treatment EGFR plasma test with brain and new metastasis were detected as independent prognostic factors for worse PFS ( P = 0.008, 0.016 and 0.028, respectively). While EGFR plasma ( P = 0.044) with bone metastasis at baseline ( P = 0.012), new metastasis ( P = 0.003), and high cfDNA concentration ( P = 0.004) serve as the worse survival factors, surgery treatment helps to prolong OS in NSCLC treated with EGFR TKI ( P = 0.012). BMA analysis identified EGFR plasma test as the strongest prognostic factor for both PFS and OS (possibility of 100% and 99.7%, respectively). Conclusions EGFR plasma test is the powerfully prognostic factor for early resistance with EGFR TKI and worse survival in NSCLC regardless of clinical characteristics.

Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

“…Univariate analyses of our results showed a negative correlation between a detectable baseline plasma EGFR ctDNA and PFS. This result is consistent with some reports performed in metastatic NSCLC patients [21][22][23][24][25]. Given that ctDNA values are correlated with tumour burden, we speculate that these patients with radiological local disease but detectable baseline plasma EGFR ctDNA may harbour a higher systemic burden and do poorly despite local radical treatment.…”

“…The protocol was later amended to allow for use of multi gene panel (gene list: ALK, BRAF, ERBB2, EGFR [exons [18][19][20][21], KRAS, MET, NRAS, PIK3CA, STK11, and TP53) NGS LiquidMARK TM test [12] on the stored frozen plasma samples.…”

An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma

“…Since fraction 6 has smaller fragments (∼140 bp) than any other fractions, it may be one reason to explain why fraction 6 shows an increased ctDNA content and thus higher sensitivity in mutation detection. Additionally, detection of EGFR mutations in plasma samples of NSCLC patients are predictive of survival and resistance to EGFR TKI (31). Therefore, our results strongly support that the enriched ctDNA in fraction 6 will increase mutation detection sensitivity and facilitate identification of tumor-specific biomarkers.…”

Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma

“…Worldwide, lung cancer is the most common cancer among men in terms of both incidence and mortality, and nearly 50% are adenocarcinoma (1, 2). The mutation status of epidermal growth factor receptor (EGFR) acts as a significant molecular feature of lung adenocarcinoma patients and sensitizing EGFR mutations including in-frame deletion of exon 19 and L858R substitute mutation of exon 21 play a critical role in predicting the sensitivity to EGFR tyrosine kinase inhibitor (EGFR-TKI) (3–5). Therefore, EGFR mutation detection is extremely valuable for the diagnosis and treatment of lung cancer.…”