Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Emmanuel Acheampong, Afaf Abed, Michael Morici, Samantha Bowyer, Benhur Amanuel, Weitao Lin, Michael Millward, Elin S Gray, Emmanuel Acheampong, Afaf Abed, Michael Morici, Samantha Bowyer, Benhur Amanuel, Weitao Lin, Michael Millward, Elin S Gray

Abstract

: Antibodies against programmed death-1 (PD-1), and its ligand, (PD-L1) have been approved recently for the treatment of small-cell lung cancer (SCLC). Although there are previous reports that addressed PD-L1 detection on tumour cells in SCLC, there is no comprehensive meta-analysis on the prevalence of PD-L1 expression in SCLC. We performed a systematic search of the PubMed, Cochrane Library and EMBASE databases to assess reports on the prevalence of PD-L1 expression and the association between PD-L1 expression and overall survival (OS). This meta-analysis included 27 studies enrolling a total of 2792 patients. The pooled estimate of PD-L1 expression was 26.0% (95% CI 17.0-37.0), (22.0% after removing outlying studies). The effect size was significantly heterogeneous (I2 = 97.4, 95% CI: 95.5-98.5, p < 0.0001).Positive PD-L1 expression was a favourable prognostic factor for SCLC but not statistically significant (HR = 0.86 (95% CI (0.49-1.50), p = 0.5880; I2 = 88.7%, p < 0.0001). Begg's funnel plots and Egger's tests indicated no publication bias across included studies (p > 0.05). Overall, there is heterogeneity in the prevalence of PD-L1 expression in SCLC tumour cells across studies. This is significantly moderated by factors such as immunohistochemistry (IHC) evaluation cut-off values, and assessment of PD-L1 staining patterns as membranous and/or cytoplasmic. There is the need for large size, prospective and multicentre studies with well-defined protocols and endpoints to advance the clinical value of PD-L1 expression in SCLC.

Keywords: meta-analysis; programmed death ligand-1; small-cell lung cancer.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of identifying eligible articles.
Figure 2
Figure 2
Forest plot of studies reporting the detection rate of programmed cell death ligand-1 (PD-L1) expression in small-cell lung cancer (SCLC). The PD-L1 detection rates and 95% CI of each study are represented with a horizontal line and the square area mirrors the point estimate of each study. A random-effect model was utilised.
Figure 3
Figure 3
Leave-one-out sensitivity plot of studies reporting the prevalence of PD-L1 expression in SCLC. Each box depicts a summary of the calculated prevalence leaving out a study. The reference shows where the original summarised prevalence lies.
Figure 4
Figure 4
Forest plot of subgroup analysis of the association between immunohistochemistry (IHC) cut-off values and prevalence of PD-L1 expression. The PD-L1 detection rates and 95% CI of each study are represented with a horizontal line and the square area mirrors the effect size of each study A random-effect model was utilised.
Figure 5
Figure 5
Forest plot of subgroup analysis of the association between the assessment of PD-L1 staining pattern in membrane+/-cytoplasm and prevalence of PD-L1 expression. The PD-L1 detection rates and 95% CI of each study are represented with a horizontal line and the square area mirrors the size effect of each study.
Figure 6
Figure 6
Forest plot of subgroup analysis of the association between the type of antibody and prevalence of PD-L1 expression. The PD-L1 detection rates and 95% CI of each study are represented with a horizontal line and the square area mirrors the size effect of each study. Highlighted in red are the antibody clones from FDA approved PD-L1 assays.
Figure 7
Figure 7
Forest plots of overall survival and PD-L1 expression in SCLC tumours. The HR and 95% CI of each study is represented with a horizontal line and the square area mirrors the size effect of each study. Pooled HR and 95% CI are depicted by diamonds. A random-effect model was utilised.

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