A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)

Yuankai Shi, Joseph Siu-Kie Au, Sumitra Thongprasert, Sankar Srinivasan, Chun-Ming Tsai, Mai Trong Khoa, Karin Heeroma, Yohji Itoh, Gerardo Cornelio, Pan-Chyr Yang, Yuankai Shi, Joseph Siu-Kie Au, Sumitra Thongprasert, Sankar Srinivasan, Chun-Ming Tsai, Mai Trong Khoa, Karin Heeroma, Yohji Itoh, Gerardo Cornelio, Pan-Chyr Yang

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.

Conflict of interest statement

Disclosure: Drs. Heeroma and Itoh are employees of AstraZeneca and hold shares in AstraZeneca. Drs. Shi, Au, Thongprasert, Srinivasan, Khoa, and Yang do not have any conflicts of interest to disclose. Dr. Tsai has received honoraria for speech from AstraZeneca, Pfizer, Roche, Eli Lilly, and Boehringer Ingelheim. Dr. Cornelio has received consultancy fees from AstraZeneca.

Figures

FIGURE 1.
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.
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.

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