Survival differences between smokers and nonsmokers with EGFR mutated non-small cell lung cancer.

Abstract

e21509 Background: Patients with epidermal growth factor receptor (EGFR) mutated lung cancer have an excellent prognosis compared to other non-small cell lung cancer (NSCLC) with no driver mutation, however, there is a wide range of survival between even a cohort with an EGFR driver mutation. Given that many patients with EGFR mutations are never smokers, it is possible that those with a smoking history have tumors with other oncogenic mutations and therefore as their tumors are less dependent on the EGFR driver, they may derive less benefit from targeted therapy. Methods: Pathology specimens of NSCLC sent for EGFR testing between January 1 2012 and December 31 2016 at Beaumont Hospital, Michigan were reviewed. If a tumor harbored a targetable EGFR mutation, the chart was queried. Inclusion criteria were EGFR exon 19 or 21 mutations, stage IV disease, at least 2 time points of follow up. Exclusion criteria included small cell histology, negative EGFR test, or inadequate information in the chart. The primary endpoint of the study was median survival. Results: Out of 329 cases identified, 40 were positive for EGFR exon 19 or 21 mutations. Of the 40 positive cases, 26 fit all inclusion criteria. Median duration of follow up was 14 months (range 0-80). Smokers represented 13/26 (50%) of cases. Death occurred in 9/13 (69%) of smokers vs 7/13 (54%) in non-smokers. Median survival was 8 mo (0-26) vs 20 mo (1-80) respectively for smokers vs non-smokers. Conclusions: This data suggests there may be a clinically relevant difference in the survival between smokers and nonsmokers who have NSCLC with an EGFR driver mutation. This may be due to the relatively low burden of alternative driver oncogene mutations in the nonsmoker’s tumors resulting in a lower likelihood of an escape mechanism for the tumor to survive. Further analysis of larger datasets with complete molecular analysis of the tumors would be informative in exploring this hypothesis. This would aid in risk stratifying patients more effectively for future clinical trials targeting the EGFR mutation and refining the prognosis in this otherwise good prognosis group.