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Purpose  Lung cancer in never smokers is recognized as a distinct molecular, clinicopathologic and epidemiologic entity. The aim of the study was to investigate the molecular profile in Swiss never smokers with lung adenocarcinoma and to correlate the mutation status with clinicopathologic and demographic patient characteristics and outcome.    Methods  One hundred thirty-eight never smokers diagnosed with lung adenocarcinoma at the University Hospital Zurich between 2011–2018 were included in the study. Data from the electronic medical records were reviewed to characterize clinicopathologic and demographic features, molecular profile, treatment and outcome.    Results  The majority of patients were female (58.7%) with a median age at diagnosis of 64.5 years (range, 27.1–94.2 years). The most common mutations were  EGFR  (58.7%) followed by  ALK  (12.3%),  TP53  (5.8%),  MET  (5.8%),  KRAS  (4.3%),  ERBB2  (4.3%),  PIK3CA  (2.9%),  BRAF  (2.2%),  ROS1  (1.4%),  RET  (1.4%), CTNNB1 (0.7%), PARP1 (0.7%), TET1 (0.7%) and PIK3CG (0.7%). Median overall survival (mOS) was 51.0 months (mo). Early clinical stage ( p  = 0.002) and treatment with targeted therapy (HR 2.53, 95% CI 1.35–4.74,  p  = 0.004) were independently associated with longer mOS. Patients with oncogenic driver mutations had significantly longer mOS (52.2 mo) compared to patients without mutations (16.9 mo) (HR 3.38, 95% CI 1.52–7.55,  p  = 0.003). Besides, patients with  EGFR  mutated (57.8 mo) or  ALK  rearranged (59.9 mo) tumors had significantly longer mOS compared to the  EGFR  wildtype (35.0 mo),  ALK  wildtype (46.5 mo) and pan-negative (16.9 mo) cohorts (HR 2.35, 95% CI 1.37–4.04,  p  = 0.002; HR 7.80, 95% CI 3.28–18.55,  p  < 0.001; HR 3.96, 95% CI 1.21–12.95,  p  = 0.023 and HR 34.78, 95% CI 3.48–34.65,  p  = 0.003).    Conclusion  Never smokers with lung adenocarcinoma display distinct clinicopathologic and molecular features and are characterized by a high incidence of targetable mutations. Never smokers with targetable mutations have significantly longer survival compared to patients without mutations.

Oncogenic driver mutations in Swiss never smoker patients with lung adenocarcinoma and correlation with clinicopathologic characteristics and outcome