Efficacy, safety and cost-effectiveness of chemo-immunotherapy combinations for recurrent or metastatic nasopharyngeal carcinoma: an updated systematic review and cost-effectiveness analysis.

Background: While toripalimab, camrelizumab and tislelizumab plus gemcitabine and cisplatin (TorGP, CamGP and TisGP) have been approved as first-line therapy for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in China, comprehensive comparisons of their relative clinical and economic value remain unavailable. Therefore, the objective of this study is to identify the most beneficial first-line treatment strategy for R/M NPC that balances efficacy, safety, and cost-effectiveness, thereby supporting informed clinical decision-making and efficient healthcare resource allocation. Methods: A comprehensive systematic search was conducted across multiple databases-including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov-for phase 3 randomized controlled trials (RCTs) evaluating chemo-immunotherapy combinations in R/M NPC, covering all records from database inception through June 20, 2025. The study protocol has been formally registered with PROSPERO under the registration number CRD42023422137. We conduct a network meta-analysis (NMA), with the primary outcomes being hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). For safety assessment, we evaluate the incidence of treatment-emergent adverse events (TEAEs). For the cost-effectiveness analysis (CEA), we develop a partitioned survival model with a 10-year time horizon and three health states: PFS, progressed disease, and death, using 3-week cycles. As a scenario analysis, we incorporate restricted cubic splines (RCS) and mixture cure model (MCM). The primary outcomes of the CEA includ quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratios (ICERs). We perform extensive sensitivity analyses to verify the robustness of our findings. Methodological rigor of incorporated RCTs was assessed utilizing the Cochrane Risk of Bias Tool (RoB 2.0). Results: Three RCTs-JUPITER-02, CAPTAIN-1st, and RATIONALE-309-collectively encompassing 815 patients, formed the basis of the NMA. Based on the surface under the cumulative ranking curve estimated relative ranking in the NMA, TisGP may have higher efficacy and safety compared with other treatments, but there is no statistical significance. In terms of CEA, based on standard parametric survival model, we add RCS and MCM as scenario analysis and yielded consistent conclusions. In the standard parametric survival model, CamGP, TorGP, and TisGP were associated with ICERs of $24,331/QALY, $18,776/QALY, and $20,762/QALY, respectively, compared to GP. Compared to CamGP, TisGP and TorGP had ICERs of $5,880/QALY and $10,567/QALY, respectively. Compared to TorGP, TisGP has ICERs of $67,564/QALY, which is higher than the willingness-to-pay (WTP) threshold of $40,354.20/QALY. As a result, TorGP is proven to be the most cost-effective option. TorGP to be cost-effective under a WTP of 3-time gross domestic product (GDP) per capita is 100%. Conclusions: In summary, while TisGP shows a clinically favorable trend in efficacy and safety, TorGP demonstrates superior cost-effectiveness with an incremental cost-effectiveness ratio well below the willingness-to-pay threshold. This finding suggests that clinicians should comprehensively evaluate individual patient characteristics when selecting treatment regimens.