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Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Emmanuel Acheampong1, Afaf Abed1,2, Michael Morici1
1School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia.
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.
Insights
This meta-analysis found that programmed death-1 ligand (PD-L1) expression in small-cell lung cancer (SCLC) tumors varies significantly. While PD-L1 expression may be a favorable prognostic factor, more research is needed to clarify its clinical value.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biomarkers
Background:
- Programmed death-1 (PD-1) and its ligand (PD-L1) inhibitors are approved for small-cell lung cancer (SCLC) treatment.
- Previous reports on PD-L1 detection in SCLC tumors exist, but a comprehensive meta-analysis is lacking.
- Understanding PD-L1 expression prevalence is crucial for optimizing SCLC immunotherapy.
Purpose of the Study:
- To conduct a meta-analysis on the prevalence of PD-L1 expression in SCLC.
- To assess the association between PD-L1 expression and overall survival (OS) in SCLC patients.
- To identify factors contributing to heterogeneity in PD-L1 expression across studies.
Main Methods:
- Systematic literature search of PubMed, Cochrane Library, and EMBASE databases.
- Inclusion of 27 studies with a total of 2792 SCLC patients.
- Statistical analysis including pooled prevalence estimation, heterogeneity assessment (I² statistic), and survival analysis (Hazard Ratio).
Main Results:
- The pooled prevalence of PD-L1 expression in SCLC was 26.0% (95% CI 17.0-37.0), with significant heterogeneity (I² = 97.4%).
- PD-L1 expression was not a statistically significant favorable prognostic factor for OS (HR = 0.86, p = 0.5880).
- Heterogeneity was influenced by immunohistochemistry (IHC) cut-off values and staining patterns (membranous/cytoplasmic).
Conclusions:
- Significant heterogeneity exists in reported PD-L1 expression prevalence in SCLC.
- Standardization of IHC evaluation methods is necessary to improve the clinical utility of PD-L1 as a biomarker in SCLC.
- Large-scale, prospective, multicenter studies are required to definitively establish the prognostic and predictive value of PD-L1 in SCLC.
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