PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis

Background: PD-L1 tumor expression has been associated with poor prognosis in a variety of solid tumors, including lung cancer, and represents a validated target for immune checkpoint inhibition in advanced malignances. It remains unknown, however, if PD-L1 can be used to predict survival in early stage, surgically treated cancers. This meta-analysis compares PD-L1 tumor expression and long term survival after surgical resection in early non-small cell lung cancer (NSCLC).

Methods: PubMed was searched to identify eligible studies that compared survival of surgically resected stage I-III NSCLC patients according to PD-L1 tumor expression. Included studies were grouped according to measurement criteria of PD-L1 expression: 1%, 5%, 50% cutoffs or H-score. Meta-analysis was performed using a linear mixed-effects model to determine overall survival (OS). I² was used as a measure of heterogeneity.

Results: There were 40 eligible studies, including 10,380 patients. Regardless of cut-off used, higher PD-L1 tumor expression was associated with worse OS [hazard ratio (HR)_1%: 1.59, 95% confidence interval (CI), 1.17-2.17; HR_5%: 1.44, 95% CI, 1.03-2.00; HR_50%: 1.52, 95% CI, 1.02-2.25, HR_H-score: 1.34, 95% CI, 1.04-1.73]. Study heterogeneity was low and not statistically significant under all PD-L1 cutoffs.

Conclusions: PD-L1 expression is consistently associated with worse survival, regardless of how it is quantified. In addition to acting as a prognostic biomarker, PD-L1 may also be used in future as a predictive biomarker for patients most likely to benefit from adjuvant immunotherapy.