Impact of EGFR and KRAS mutations on survival in 1,000 patients with resected lung adenocarcinoma.

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7011 Background: Previous studies have reported trends toward improved overall survival in patients with resected adenocarcinoma of the lung and EGFR mutation compared to patients without detectable mutation (Marks, et al, 2008). Some studies demonstrated no difference in survival, but did not classify patients by KRAS mutation status. Reports on the prognostic significance of KRAS mutations have been inconsistent. In this study, we evaluated the prognostic significance of EGFR and KRAS mutations in 1,000 patients. Methods: Clinical information was prospectively collected on patients with completely-resected stage I-III lung adenocarcinoma at Memorial Sloan-Kettering Cancer Center who had surgery between Jan 2002–Oct 2009. EGFR mutation (exon 19 deletion or L858R) was determined by PCR, KRAS mutation was determined by sequencing. Overall survival from the date of surgery was analyzed using Kaplan-Meier and Cox regression analyses. Patients who received an EGFR tyrosine kinase inhibitor (TKI) during their treatment were excluded (N=131). Results: 1,000 patients (618 women) with stage I (732), stage II (121), and stage III (147) were evaluated. Median follow-up was 16 months. After adjustment for stage, there was a trend towards better survival in EGFR mutation-positive patients (N=145) compared to wildtype (N=588), HR 0.76 95% CI 0.45 to 1.30, p=0.3. There was a trend towards worse survival in patients with KRAS mutation (N=267) compared to wildtype, HR 1.20 95% CI 0.83 to 1.70, p=0.4. Three year survival proportions for each group were: EGFR mutation 80% (95% CI 0.67 to 0.89), KRAS mutation 73% (95% CI 0.63 to 0.81), wildtype 73% (95% CI 0.69 to 0.78). Conclusions: This is the largest cohort of patients with resected lung adenocarcinoma reported for these mutations (N=1,000). Despite excluding patients who received perioperative EGFR TKI, the trend for patients with EGFR mutation is towards better survival compared to wildtype. A trend for survival decrement in patients with KRAS mutations was less apparent. Longer follow-up is required to determine whether these trends are statistically significant. Future analyses will include assessments of the impact of perioperative EGFR TKI and EGFR TKI at recurrence. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Molecular MD