A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER)

Abstract

Introduction:PIONEER (NCT01185314) was a prospective, multinational, epidemiological study of epidermal growth factor receptor (EGFR) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma.Methods:Eligible patients (aged ≥20 years) had untreated stage IIIB/IV adenocarcinoma. The EGFR mutation status (primary end point: positive, negative, or undetermined) of tumor samples (biopsy, surgical specimen, or cytology) was determined (Scorpion amplification refractory mutation system). EGFR mutation frequency was calculated and compared between demographic and clinical subgroups.Results:Of 1482 patients from seven Asian regions, 43.4% of patients were female, median age was 60 years (range, 17–94), and 52.6% of patients were never-smokers. EGFR mutation status was evaluable in tumors from 1450 patients (97.8%) (746 [51.4%] positive; 704 [48.6%] negative). Country, sex, ethnicity, smoking status, pack-years (all p < 0.001), disease stage (p = 0.009), and histology type (p = 0.016) correlated significantly with EGFR mutation frequency. Mutation frequency was 61.1% in females, 44.0% in males; lower in patients from India (22.2%) compared with other areas (47.2%–64.2%); highest among never-smokers (60.7%); and decreased as pack-year number increased (>0–10 pack-years, 57.9%; >50 pack-years, 31.4%) (similar trend by sex). Ethnic group (p < 0.001) and pack-years (p < 0.001) had statistically significant associations with mutation frequency (multivariate analysis); sex was not significant when adjusted for smoking status.Conclusion:PIONEER is the first prospective study to confirm high EGFR mutation frequency (51.4% overall) in tumors from Asian patients with adenocarcinoma. The observed high mutation frequency in demographic/clinical subgroups compared with white populations suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma, even males and regular smokers, among Asian populations.

The Role of Smoking Status on the Progression-Free Survival of Non-Small Cell Lung Cancer Patients Harboring Activating Epidermal Growth Factor Receptor (EGFR) Mutations Receiving First-Line EGFR Tyrosine Kinase Inhibitor Versus Platinum Doublet Chemotherapy: A Meta-Analysis of Prospective Randomized Trials

“…More importantly, the percentage of EGFRm among heavy Asian smokers (.50 pack years) in the same study was as high as 31.4% [27]. Furthermore 20.7% of the EGFRm patients were active smokers [27].…”

“…More importantly, the percentage of EGFRm among heavy Asian smokers (.50 pack years) in the same study was as high as 31.4% [27]. Furthermore 20.7% of the EGFRm patients were active smokers [27]. It is unlikely that these EGFRm patients with .50 pack years of smoking had the same genetic background in their tumors as EGFRm patients who were never-smokers.…”

Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis

“…Lung adenocarcinoma patients are often more sensitive to treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) following the failure of first-line chemotherapy, which may account for the differences in survival (11). Furthermore, a previous prospective study determined a higher EGFR mutation frequency rate (51.4% overall) in Asian patients exhibiting adenocarcinoma tumors compared with squamous cell carcinoma tumors (12). In another study, although EGFR mutations were present in cases of lung squamous cell carcinoma, indicating that these patients would receive some benefit from EGFR-TKI treatment, a poorer curative effect was observed in the squamous carcinoma patients compared with the adenocarcinoma patients (13).…”

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

“…Epidermal growth factor receptor (EGFR) mutation is the most common molecular driver alteration that occurred in 20 to 30 percent of NSCLC patients. 2 The treatment strategies blocking EGFR pathway in EGFR-mutant lung cancer, which effectively repress tumor by inhibition of driver oncogenes, establish a remarkable example of molecular targeted therapies. 3 Other molecular alterations, such as KRAS, BRAF mutations and ALK translocations have also been defined as "driver mutations" in lung cancer successively.…”