Gastric cancer remains a prevalent malignant tumor worldwide with relatively poor prognosis, posing a serious threat to human health (1). According to statistics from the International Agency for Research on Cancer (IARC), there were approximately 968,000 new gastric cancer cases and 660,000 deaths globally in 2022, with both incidence and mortality ranking fifth among all cancers (2). Over 70% of new gastric cancer cases occur in Asia, with about 50% concentrated in Eastern Asia, predominantly in China (3). China accounts for 37.0% of global gastric cancer cases and 39.4% of related deaths. The established first-line regimen for unresectable advanced gastric cancer and GEJ malignancies [which account for over 70% of total gastric cancer cases in China (4)] consisted of fluoropyrimidine-based chemotherapy combined with platinum agents, yielding suboptimal survival outcomes with overall survival (OS) of only 1 year (5, 6). Novel developments in immune checkpoint blockade therapy, with particular focus on PD-1/PD-L1 pathway inhibition, have yielded encouraging therapeutic outcomes (7–9).

Sugemalimab is a fully human IgG4 (s228p) monoclonal antibody that specifically binds PD-L1 while preserving FcγRI engagement. This unique design facilitates macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) through cross-linking of PD-L1 + tumor cells with FcγRI-expressing effector cells (10). GEMSTONE 303 was a Phase 3, randomized, double-blind, placebo-controlled study conducted across 54 clinical trial sites in China (11). This study evaluated the safety and efficacy of sugemalimab combined with capecitabine and oxaliplatin (CAPOX) compared to placebo plus CAPOX in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose programmed death-ligand 1 (PD-L1) combined positive score (CPS) was 5 or higher. The newly released results demonstrated that, compared to placebo plus CAPOX, sugemalimab combined with CAPOX significantly improved both median progression-free survival [15.6 months vs. 12.6 months, hazard ratio (HR) = 0.75, 95% confidence interval (CI) (0.61, 0.92)] and median overall survival [7.6 months vs. 6.1 months, HR = 0.66, 95% CI (0.54, 0.81)]. Additionally, the incidence of grade ≥3 treatment-related adverse events was similar between the two groups (53.9% vs. 50.6%), with manageable safety, indicating significant clinical benefits of this treatment regimen.

Given that the price of sugemalimab may impose a significant economic burden on gastric cancer patients and China’s healthcare system, it is necessary to evaluate its cost-effectiveness under the current pricing. Therefore, based on the GEMSTONE 303 trial, this study employs a three-state partitioned survival model from the perspective of China’s healthcare system to explore its reasonable pricing in alignment with its clinical value, aiming to provide a reference for future national medical insurance negotiations.

The present study evaluated the cost-effectiveness of sugemalimab combined with chemotherapy as a first-line treatment for advanced gastric cancer in China, utilizing a partitioned survival model based on data from the GEMSTONE-303 trial. The results demonstrated that, despite providing incremental clinical benefits (0.12 QALYs), the regimen’s high incremental cost (¥226,866.55) resulted in an ICER of ¥1,890,554.58 per QALY, far exceeding China’s WTP threshold (¥287,391). Although the GEMSTONE-303 trial demonstrated significant improvements in PFS and OS, these benefits primarily resulted from prolonged disease stabilization rather than a substantial enhancement in quality of life, which may have reduced the QALY weighting. Furthermore, long-term survivors receiving immunotherapy may experience immune-related adverse events, potentially diminishing utility values. Consequently, the ICER was considerably higher than the predefined WTP threshold. This finding suggests that, under current pricing, sugemalimab is not a cost-effective option for advanced gastric cancer treatment within China’s healthcare system.

The robustness of these conclusions was confirmed through sensitivity analyses. One-way sensitivity analysis identified the utility values of PD and PFS states, as well as the cost of sugemalimab, as the most influential parameters on the ICER. However, even under extreme variations of these parameters, the regimen remained economically unviable. Probabilistic sensitivity analysis further reinforced this outcome, showing a 0% probability of cost-effectiveness at WTP thresholds below ¥420,000. Only at an unrealistically high WTP (¥2,000,000) did the sugemalimab regimen achieve parity with chemotherapy alone, highlighting the need for substantial price reductions to align with China’s economic realities.

These findings have significant implications for healthcare policy and clinical practice. While the GEMSTONE-303 trial established the clinical efficacy of sugemalimab, its high cost poses a barrier to widespread adoption in resource-limited settings like China. Potential strategies to improve cost-effectiveness include price negotiations, patient assistance programs, or biomarker-driven approaches targeting subpopulations with higher PD-L1 expression (e.g., CPS ≥ 10), who may derive greater benefit. Such measures could enhance the regimen’s value proposition and facilitate its inclusion in national reimbursement schemes.

Our study has several notable strengths. First, to our knowledge, this is the first comprehensive cost-effectiveness analysis of sugemalimab combined with chemotherapy for advanced gastric cancer in the Chinese healthcare context, providing crucial evidence for policymakers and clinicians. Second, our model utilized robust clinical data from the GEMSTONE-303 trial, ensuring that the survival and efficacy inputs were derived from a high-quality randomized controlled trial. Additionally, we conducted extensive sensitivity analyses (both one-way and probabilistic), which confirmed the stability of our findings across a wide range of parameter uncertainties.

This study has the following limitations: (1) The PFS and OS curves were extrapolated by fitting parametric distributions. Although this approach can predict survival trends beyond the follow-up period of the GEMSTONE-303 trial, the extrapolated survival data rely on assumptions inherent to parametric models. Consequently, the actual survival benefits may differ from the model predictions. (2) The original study did not specify the exact second-line chemotherapy regimen. In this analysis, subsequent treatments were selected based on clinical guidelines, which may not fully reflect real-world prescribing practices. (3) Only grade ≥3 adverse reactions with an incidence >3% were included. While this may introduce discrepancies compared to actual clinical outcomes, the one-way sensitivity analysis demonstrated that the costs of managing adverse events had minimal impact on the results. Thus, this limitation is unlikely to alter the study’s conclusions. (4) Findings are specific to China’s healthcare pricing and reimbursement policies. The cost-effectiveness of sugemalimab may differ in countries with higher willingness-to-pay thresholds or alternative drug pricing structures. Despite these limitations, our study provides valuable insights into the economic viability of sugemalimab for advanced gastric cancer in China.

In conclusion, while sugemalimab represents a promising therapeutic advance for advanced gastric cancer, its current cost renders it economically unsustainable in China. Policymakers and manufacturers must collaborate to develop pricing strategies that balance innovation with affordability, ensuring patient access without overburdening the healthcare system. This study provides a critical foundation for such discussions and underscores the importance of economic evaluations in guiding healthcare decision-making.