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.

FIGURE 1.

Study flow diagram. ^aTwo patients had major protocol deviations: one patient did not have histologically or cytologically confirmed NSCLC, and one patient had received previous treatment for NSCLC. Three patients were <20 years old and therefore violated the study inclusion criteria. This deviation was considered to be minor and these patients were subsequently included in the PP population. ^bFour patients had tumor samples that were not tested for EGFR mutations: two biopsy samples were lost after pathological reading, one sample did not have a clot for preparing a tissue block, and the DNA concentration of one block was insufficient for testing. EGFR, epidermal growth factor receptor; NSCLC, non–small-cell lung cancer; PP, per-protocol population.

FIGURE 2.

Combined effect of sex and (A) smoking status and (B) pack-years on frequency of EGFR mutation (PP population). A, p values for logistic regression model. Smoking history definitions: never-smoker (patients who had never smoked cigarettes in their lifetime); ex-smoker (patients who had previously smoked but no longer smoked); occasional smoker (patients who smoked, but not every day); regular smoker (patients who smoked every day). B, p values for logistic regression model. EGFR, epidermal growth factor receptor; PP, per-protocol.