Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers

Abstract Introduction: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. Methods: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients’ smoking history was examined. Light, moderate and heavy smokers were patients who had smoked <20, 20-39, and >40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as follows: high expression (TPS ≥50%), low expression (TPS 1% - 49%) and no expression (TPS <1%). Results: 101 (52.9%) of 191 patients were never smokers. EGFRmutations were more common in never smokers [65 (64.4%) of 101 patients] than in smokers [16 (17.8%) of 90 patients] (P<0.0001). A higher proportion of smokers had high PD-L1 expression [24 (26.7%) of 90] compared to never smokers [14 (13.9%) of 101] (P=0.042). High PD-L1 expression was seen in 32 of 110 patients (29.1%) with EGFRwild-type tumors but only in 6 of 81 (7.4%) patients with tumors harbouring sensitising EGFR mutations (P<0.0001). Among the 90 smokers, a higher proportion of heavy smokers [19 (35.8%) of 53] than non-heavy smokers [5 (13.5%) of 37] had high PD-L1 expression (P = 0.034). Conclusions: High PD-L1 expression in NSCLC is more common in smokers than in never smokers, in EGFRwild-type than EGFR-mutant NSCLC and in heavy smokers among smokers.