Molecular Epidemiology of EGFR Mutations in Asian Patients with Advanced Non-Small-Cell Lung Cancer of Adenocarcinoma Histology – Mainland China Subset Analysis of the PIONEER study

Abstract

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged.

Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011–2015

“…Our study showed that EGFR mutation rate reached 66% in ADC females and 37% in ADC males. This data was similar with the results of other studies (16)(17)(18).…”

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

“…In the present study, 40.3% (58/144) of patients exhibited EGFR mutations, values close to those obtained by Shi et al and Wu et al (43,44). In the present study, EGFR mutations appeared more frequently in women than in men (60.9 vs. 43.8%, P=0.04), more frequently in non-smokers than in smokers (62.8 vs. 34.5%, P=0.001), as expected (43,(45)(46)(47).…”

“…The frequency of EGFR mutations in lung adenocarcinoma was 51.4% (74/144) in the present study, which was concordant with that in previous studies conducted in Asia (3,42,43). In the present study, 40.3% (58/144) of patients exhibited EGFR mutations, values close to those obtained by Shi et al and Wu et al (43,44).…”

Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations

“…The notion that somatic genetic factors may influence tumor biology differentially across distinct ancestral backgrounds is exemplified by high EGFR mutation rates in patients of Asian ancestry with non-small cell lung adenocarcinoma (up to 50% of patients), compared to patients of European ancestry (10–15% of cases) (7). Large-scale genomic characterization studies are predominated by tumor samples from patients of European ancestry (8).…”