EGFR-plasma mutations in prognosis for non-small cell lung cancer treated with EGFR TKIs: A meta-analysis.

BACKGROUND: The plasma-based epidermal growth factor receptor (EGFR) mutation testing is approved recently to use in clinical practice. However, it has not been used as a prognostic marker yet because of contradictory results. AIM: This meta-analysis aims to clarify the role of the EGFR-plasma test in prognosis for non-small cell lung cancer (NSCLC) who have mutant tumors and receive EGFR tyrosine kinase inhibitors (TKIs). METHODS AND RESULTS: The PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases were searched for relevant studies by April 10, 2021. The hazard ratio (HR) from reports was extracted and used to assess the correlation of EGFR-plasma status with progression-free survival (PFS) and overall survival (OS). A total of 35 eligible studies with 4106 patients were enrolled in the final analysis. Patients with concurrent EGFR mutations in pretreatment plasma have shorter PFS (HR = 2.00, 95% confidence interval [CI]: 1.73-2.31, p < .001) and OS time (HR = 2.31, 95% CI: 1.89-2.83, p < .001) compared to the tumor-only mutation cases. Besides, the persistence of EGFR-activating mutations in post-treatment plasma is associated with worse PFS (HR = 3.84, 95% CI: 2.96-4.99, p < .001) and OS outcome (HR = 3.22, 95% CI: 2.35-4.42, p < .001) compared to others. Notably, the prognostic value of the EGFR-plasma test is also validated in treatment with third-generation EGFR TKI and significance regardless of different detection methods. CONCLUSION: The presence of EGFR-plasma mutations at pretreatment and after EGFR TKI initiation is the worse prognostic factor for PFS and OS in NSCLC.

Smoking habit and chemo-radiotherapy and/or surgery affect the sensitivity of EGFR plasma test in non-small cell lung cancer.

OBJECTIVE: This study aimed to identify the influential factors for the sensitivity of epidermal growth factor receptor (EGFR) plasma test in non-small cell lung cancer (NSCLC). The mutations were detected in tumor tissue and matched plasma samples from 125 newly diagnosed adenocarcinoma, clinical-stage IIIB-IV patients, and compared the diagnostic values of EGFR plasma test between groups of clinical characteristics. The influential factors for the sensitivity were identified and assessed by logistic regression. RESULTS: EGFR mutations were detected in 65 (52.0%) tumor tissue and 50 (40.0%) matched plasma samples (P = 0.028). Compared to the tissue method, the concordance rate, sensitivity, and specificity of the EGFR plasma test were 86.4%, 75.4%, and 98.3%, respectively. Notably, we found that sensitivity of the test is higher in non-smokers (84.1%) compared to smokers (57.1%, P = 0.018), and in treatment naïve subjects (85.7%) compared to whom undergone chemo-radiotherapy with/without surgery before testing (56.5%, P = 0.009). Furthermore, the highest sensitivity was attained in patients without these two factors (90.3%), whilst the lowest value was noted in those with both factors (40.0%, P = 0.004). The multivariable analysis confirmed that smoking habit and treatment history have independently negative impacts on sensitivity (OR = 0.24, P = 0.019, and OR = 0.36, P = 0.047, respectively).

Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer.

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population. Although genetic analysis of tumor tissue is often used to detect mutations in cancer genes, the invasiveness and limited accessibility hinders its application in large-scale population studies. Here, we used ultra-deep massive parallel sequencing of plasma cell free DNA (cfDNA) to identify the mutation profiles of 265 Vietnamese patients with advanced non-small cell lung cancer (NSCLC). Compared to a cohort of advanced NSCLC patients characterized by sequencing of tissue samples, cfDNA genomic testing, despite lower mutation detection rates, was able to detect major mutations in tested driver genes that reflected similar mutation composition and distribution pattern, as well as major associations between mutation prevalence and clinical features. In conclusion, ultra-deep sequencing of plasma cfDNA represents an alternative approach for population-wide genetic profiling of cancer genes where recruitment of patients is limited to the accessibility of tumor tissue site.

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population.

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

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

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.