Soluble PD-L1 as a Predictive Biomarker in Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: We performed a meta-analysis to evaluate the association between soluble PD-L1 (sPD-L1) and survival outcomes and treatment response in lung cancer. Methods & methods: Eligible studies were obtained by searching PubMed, EMBASE and Web of Science. Pooled effect estimates were calculated for overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Results: Twelve eligible studies with 1188 lung cancer patients were included. High sPD-L1 was significantly associated with worse OS (hazard ratio [HR] = 2.20; 95% CI: 1.59–3.05; p < 0.001) and PFS (HR = 2.42; 95% CI: 1.72–3.42; p < 0.001) in patients treated with immune checkpoint inhibitors (ICIs). Meanwhile, high sPD-L1 predicted worse OS (HR = 1.60; 95% CI: 1.31–1.96; p < 0.001) and lower ORR (odds ratio = 0.52; 95% CI: 0.35–0.80; p = 0.002) in patients treated with non-ICI therapies. Conclusion: sPD-L1 is a potential predictive biomarker of lung cancer.

Lay abstract

PD-L1 is a molecule that may suppress immune response to tumor by binding to its receptor PD-1. Agents blocking PD-L1/PD-1 pathway have greatly improved survival in many cancer patients. However, biomarkers that help select patients who can respond to these agents versus those who cannot are important. The soluble form of PD-L1 (sPD-L1) in peripheral blood (sPD-L1) can be easily detected. By pooling available evidence via meta-analysis, we find that lung cancer patients with high sPD-L1 level are less likely to response to anti-PD-L1/PD-1 antibodies, may progress earlier and have a shorter survival time than those with lower sPD-L1 level after treatment. Thus, sPD-L1 can be used as a biomarker predicting treatment response and survival in lung cancer. Yet some issues – for example, the cutoff and standard detection of sPD-L1 – need to be resolved for its clinical utility.

Keywords::

• lung cancer
• meta-analysis
• objective response rate
• overall survival
• soluble PD-L1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2021-0641

Financial & competing interests disclosure

This work was supported by Beijing Jishuitan Hospital Nova Program (XKXX201815). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Beijing Jishuitan Hospital Nova Program (XKXX201815). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.