Epidermal growth factor receptor (EGFR) mutation testing in non-small cell lung cancer (NSCLC) patients (pts)

Abstract

7177 Background: Somatic mutations in EGFR are associated with response to therapy and prolonged overall survival (OS) of NSCLC pts treated with tyrosine kinase inhibitors (TKI). We began EGFR mutation screening in 2004 with a CLIA certified test. We determined the characteristics of pts tested, EGFR mutations identified, and analyzed response to therapy and OS. Methods: We performed a retrospective cohort study of all NSCLC pts referred for EGFR testing over 1 year. Samples underwent direct sequence analysis of EGFR exons 18–24. We used multivariable logistic regression models to examine associations between mutation and pt characteristics. We used chi-square tests to assess differences in response to therapy by EGFR status and analyzed OS with Cox proportional hazard models, adjusting for age, gender and stage. Results: We screened 269 NSCLC pts for EGFR mutations, including 188 (71%) with unresectable disease and 245 (91%) with adenocarcinoma. Mutations were identified in 62 (23%) pts. 15 samples (6%) yielded insufficient DNA for testing. Mutation was more likely in the 59 never-smokers compared to the 185 ever-smokers [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.5–9.2]. Each added pack-year of smoking history lowered the odds of mutation by 5% (OR 0.95, 95% CI 0.94–0.97). Mutation was more likely in the 12 Asians than in the 212 of all other races (OR 3.7, 95% CI 1.1–12.0). In multivariable analyses, pack-years of smoking remained predictive of mutation (OR 0.96, 95% CI 0.94–0.99). Among 44 pts with unresectable disease undergoing subsequent TKI therapy, the 20 EGFR positive pts had an increased response rate (RR) compared to the 24 EGFR negative pts (60% v. 4%, p < 0.0001). In 27 pts given subsequent chemotherapy, RR was 33% and did not differ by EGFR status. Median follow-up was 9.8 months (mo) (range 0.2–135.8 mo). Among pts with unresectable disease, median OS is estimated to be 22.7 mo in EGFR negative pts and is not reached in EGFR positive pts (HR 0.22, 95% CI 0.80–0.63). Conclusions: Sequencing EGFR for somatic mutations is feasible in routine care of NSCLC pts. 23% of screened pts tested positive, and never smoking was the strongest predictor of mutation. Among patients with unresectable disease, EGFR mutation was associated with an increased RR to TKI therapy and OS. [Table: see text]