Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation

Background: Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. Objectives: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. Design: A systematic review and economic evaluation. Data sources and methods: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Results: Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Conclusion: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab.