Effect of Smoking History on NSCLC with EGFR Mutation

EGFR-mutant non-small cell lung cancer (NSCLC) in patients with a smoking history may be associated with a trend to higher non-synonymous tumor mutation burden (TMB), according to a study to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (June 1-5, 2018; Chicago, IL).

EGFR-mutant NSCLC mainly occurs in non-smoking patients, but most series report 20% to 30% of cases in current of previous smokers. Borad molecular profiling of EGFR-mutant NSCLC in patients with a smoking history has not been reported.

Hadas Sorotsky, MD, Princess Margaret Cancer Centre (Toronto, ON), and colleagues assessed the effect of prior smoking history on the molecular profile of EGFR-mutant NSCLC. 

Researchers molecularly profiled surgically resected primary EGFR exon 19 or 21 mutated NSCLC tumors from 108 patients using whole exome sequencing. Alignment and variant discovery analysis were performed according to GATK best practices workflow; 87 sequenced to a mean coverage of 65.1x. Demographics and outcomes were compared for smokers and non-smokers and by mutation profile. 

Researchers noted that 63 of the patients were non-smokers and 24 were smokers. Of the 87 patients, 52% were stage I, 20.5% were stage II, and 27.5% were stage III+. Smoking was associated with male sex and non-Asian ethnicity but not with age, stage, or EGFR exon 19/20 subtype. 

Additionally, researchers reported that multiple driver mutations occurred in tumors of 25% smokers and 23.8% non-smokers. TP53/EGFR co-mutation occurred in 57.9% smokers and 46.2% non-smokers. The total non-synonymous TMB was higher in smokers, with a median of 175.35 in smokers compared to 155.31 in non-smokers. The strongest prognostic factor for overall survival (OS) and disease-free survival (DFS) was stage. 

Results from univariate analysis found that there was a trend to shorter OS in smokers. Smoking within 10 years of NSCLC diagnosis was associated with shorter DFS, but not OS. Neither EGFR-mutant subtype nor TP53/EGFR co-mutation was associated with DFS or OS. High TMB was associated with shorter DFS and OS. Researchers acknowledged TMB was still significant for DFS after adjusting for smoking status.

“EGFR-mutant NSCLC in smokers is associated with a trend to higher non-synonymous TMB,” authors concluded. “Stage remains the strongest prognostic factor, but TMB appears to have a greater effect on survival outcomes than smoking status.”—Janelle Bradley