Utility of various programmed death-ligand 1 (PD-L1) assays in predicting the clinical benefit of immune checkpoint inhibitors in PD-L1-expressing non-small-cell lung cancer patients: a systematic review

Background: Immune checkpoint inhibitors (ICIs) targeting the programmed death ligand 1 (PD-L1)/programmed death-1 pathway are a mainstay for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC). Although some benefit has been observed in patients with low or no PD-L1 expression, ICIs are particularly recommended for those with PD-L1 expressing tumors. The limited availability of companion diagnostic (CDx) assays poses challenges for clinicians. Despite high analytical concordance among PD-L1 assays, the ability of alternative (non-comparison) assays to predict the clinical benefit of ICIs in the respective study populations has not been confirmed. This systematic literature review assessed whether alternative PD-L1 assays can predict the clinical benefit of ICI monotherapy for advanced/metastatic NSCLC with PD-L1 expression. Methods: Studies were sourced from PubMed and Google Scholar up to December 20, 2023. Included studies analyzed PD-L1 expression of patients with NSCLC treated with ICI monotherapy, reporting clinical outcomes [objective response rates (ORRs), progression-free survival (PFS), or overall survival (OS)]. Results: From 2,239 titles, four relevant trials (N=1,364) were included: two randomized controlled trials of atezolizumab, and two retrospective studies of nivolumab. These trials indicated that the PD-L1 22C3 pharmDx and Ventana PD-L1 SP263 assays may predict the benefit of atezolizumab in patients with NSCLC. Conclusions: These results may expand the therapeutic options for patients with PD-L1-expressing advanced/metastatic NSCLC using alternative PD-L1 assays. This review was limited by different patient populations, small numbers, possible inter-pathological discordance, and study heterogeneity. Evidence for nivolumab, pembrolizumab, or durvalumab remains inconclusive.