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

Abstract

ObjectiveTo assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC).MethodWe 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.ResultsA 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.ConclusionsPD-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.

Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations

“…PD‐L1 expression levels may affect the clinical benefit of ICI. In the combined analysis of 15 reported studies, EGFR ‐mutated tumors showed low PD‐L1 expression in tumors and recent studies demonstrated that PD‐L1 expression levels were associated with EGFR mutation status . However, in this study, PD‐1/PD‐L1 expression levels were not significantly different between the 2 groups with and without EGFR mutations.…”

Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

“…PD-L1 positivity was significantly lower in EGFR -mutant LUADs than in those with wild-type EGFR [ 84 ], and PD-L1-positive LUADs carrying EGFR mutations were observed in only 9% of all EGFR -mutant LUADs [ 85 ]. Concordantly, recent meta-analyses have revealed that EGFR mutations were associated with decreased expression of PD-L1 [ 86 , 87 , 88 ]. Thus, from the perspective of a negative correlation between PD-L1 positivity and EGFR mutation status, it is likely that anti-PD-1/PD-L1 therapy has limited activity for EGFR -mutant NSCLCs.…”

“…Furthermore, Roussel et al described a higher frequency of tumors combining positive PD-L1 expression and infiltration by intratumoral CD8+ T cells or PD-1+CD8+ T cells in ALK -rearranged LUADs compared to those with EGFR mutation or those with wild-type EGFR / KRAS and non- ALK rearrangement [ 94 ]. By contrast, meta-analyses have not shown significant correlations between ALK rearrangement and PD-L1 expression [ 87 , 88 ].…”

“…Clinicopathological studies have indicated the positive correlation between KRAS mutations and PD-L1 expression in NSCLC [ 80 , 85 , 87 , 88 , 96 , 98 , 99 , 100 ]. Scheel et al reported that KRAS -mutated NSCLC tumors exhibited a higher positivity of PD-L1 expression [ 98 ].…”

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

“…Besides, mEGFR is relevant to low TMB and compromised tumor-specific immune response [ 78 ]. In contrast to mEGFR , meta-analysis revealed that NSCLC patients harboring KRAS mutation are more likely to belong to PD-L1 positive subtype [ 80 ]. And Coelho MA et al found that hyperactive KRAS enhanced stability of PD-L1 mRNA by MEK-ERK signal pathway [ 81 ].…”