Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis

Abstract

Background To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs). Material and methods We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach. Results We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59–3.66, p < .001; WMD in RMPFST6: −1.01, 95% CI: −1.65 to −0.37, p = .002; WMD in RMPFST12: −2.64, 95% CI: −4.40 to −0.88, p = .003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, p = .069; WMD in RMPFST6: −1.23 vs −0.07, p = .005; WMD in RMPFST12: −3.29 vs −0.12, p = .003). The quality of summarized evidence was judged to be low. Conclusion There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs.