Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas
Cancer, 05/21/2012

Paik PK et al. – Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history.

• In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated.
• Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method.
• Group comparison was performed with log-rank tests and Cox proportional hazards methods.

• Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001).
• Among never-smokers and former/current smokers, the prognosis differed significantly by genotype.
• Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype.