Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis

Objective: To assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC).

Method: We performed a meta-analysis of 26 studies (7541 patients) which were published from 2015 to 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated to describe the correlation. Subgroup analysis was performed based on population characteristics, types of PD-L1 antibodies and quality of individual studies.

Results: A lower frequency of PD-L1 positivity was observed in NSCLCs harboring EGFR mutation (OR: 0.64, 95% CI, 0.45-0.91, p = 0.014). A negative correlation was also found at 1% (OR: 0.35, 95% CI, 0.22-0.55, p = 0.000) and 50% (OR: 0.33, 95% CI, 0.14-0.81, p = 0.015) cutoff for PD-L1 positive, elderly age group (OR: 0.56, 95% CI, 0.35-0.89, p = 0.013), female dominant group (OR: 0.55, 95% CI, 0.29-0.94, p = 0.030) and smoker dominant group (OR: 0.52, 95% CI, 0.29-0.96, p = 0.035). No significant differences in PD-L1 expression were observed among patients with different ALK, BRAF, HER2, PIK3CA status and MET expression level. Higher level of PD-L1 was found in tumors with KRAS mutation (OR: 1.45, 95% CI, 1.18-1.80, p = 0.001). PD-L1 expression level was not significantly different between triple (EGFR/ALK/KRAS) wild type NSCLCs and those with EGFR/ALK/KRAS mutation.

Conclusions: PD-L1 expression in EGFR mutated NSCLCs were lower than those in EGFR wild type NSCLCs, while tumors with KRAS mutation showed higher levels of PD-L1.