Efficacy and Safety of Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Checkpoint Inhibitors in Patients With Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Meta-analysis

Abstract

AimsThe aim of this systematic review with meta-analysis was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and methodsWe searched PubMed, Embase and Cochrane Library until 1 July 2022 for mCRPC trials testing PD-1/PD-L1 checkpoint inhibitors. We measured the efficacy and safety using overall survival, progression-free survival (PFS), overall response rates (ORR), prostate-specific antigen (PSA) response rate or treatment-related adverse events (TRAEs). When possible, data were meta-analysed. ResultsThirteen studies involving 2533 participants were included in this meta-analysis. The pooled hazard ratio for overall survival was 0.81 (95% confidence interval 0.42–1.20, I2 = 80.3%, PHeterogeneity＜0.001) and for PFS was 0.65 (95% confidence interval 0.38–0.92, I2 = 72.2%, PHeterogeneity = 0.013). Furthermore, better ORR (relative risk = 2.77, 95% confidence interval 1.25–6.13, I2 = 0%, PHeterogeneity = 0.699) was found in PD-L1-expressing tumours. However, no statistical trends between PD-L1 status on PSA response rate (relative risk = 0.79, 95% confidence interval 0.5–1.25, I2 = 0%, PHeterogeneity = 0.953) and tumour mutational burden on ORR (relative risk = 2.53, 95% confidence interval 0.49–13.12, I2 = 74.5%, PHeterogeneity = 0.02) were observed. The pooled proportions of TRAEs and ≥ grade 3 TRAEs were 85.1% (95% confidence interval = 71.7–98.5%) and 31.6% (95% confidence interval = 18.9–44.4%), respectively. ConclusionsThis meta-analysis showed that among selected populations of men with mCRPC, anti-PD-1/PD-L1 combination treatment may significantly increase the PFS benefits. However, overall survival in mCRPC warrants further testing.