OBJECTIVE To evaluate the cost-effectiveness of zolbetuximab combined with chemotherapy as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer from the perspective of China’s healthcare system. METHODS Based on individual data from the GLOW clinical trial involving CLDN18.2-positive and HER2-negative patients with advanced gastric cancer， a comparison was made between the zolbetuximab combined with chemotherapy regimen and the chemotherapy alone regimen. A dynamic Markov model was employed for simulation， with a cycle length of 21 days and a time horizon of ten years. A cost-utility analysis was employed， with both costs and health outcomes discounted at an annual rate of 5%. The primary outcome measures included total cost， quality-adjusted life years （QALY） and incremental cost-effectiveness ratio （ICER）， with the willingness-to-pay （WTP） threshold set at three times China’s per capita gross domestic product in 2024 （287 247 yuan/QALY）. One-way analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Furthermore， scenario analysis and threshold analysis were conducted to explore the impact of drug price adjustments on cost-effectiveness and the threshold price. RESULTS Compared with the chemotherapy alone regimen， the ICER of zolbetuximab combined with chemotherapy was 2 611 943.00 yuan/QALY. One-way sensitivity analysis indicated that the utility value of the progression free survival， the cost of zolbetuximab and body surface area were the three most influential parameters affecting the ICER. The results of the probabilistic sensitivity analysis showed that when the WTP threshold was set at 2 617 450 yuan/QALY， the probability that the combined regimen was cost-effective approached 50%. Scenario analysis revealed that only when the price of zolbetuximab was reduced to 10% of the baseline price did the ICER of the combined regimen fall below the aforementioned WTP threshold. Threshold analysis further indicated that when the unit price of zolbetuximab dropped to 3.81 yuan/mg， the probability of the combination regimen being cost-effective was approximately 50%. CONCLUSIONS From the perspective of China’s healthcare system， zolbetuximab combined with chemotherapy regimen as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer is not cost-effective compared with chemotherapy alone regimen. When the unit price of zolbetuximab drops to 3.81 yuan/mg or below， the regimen becomes cost-effective.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

OBJECTIVE To evaluate the efficacy and safety of first-line treatments regimens for human epidermal growth factor receptor 2 （HER2）-positive advanced gastric cancer. METHODS Computer searches were conducted on databases such as Web of Science， Embase， CNKI， and VIP in both Chinese and English， and abstracts of papers from the annual meetings of the European Society of Oncology and the American Society of Clinical Oncology were screened. Collected randomized controlled trials （RCTs） on first-line treatment for HER2-positive advanced unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients， with a retrieval period from database establishment until April 1， 2025. A network meta-analysis was conducted by two researchers who independently screened literature， extracted data， and evaluated the risk of bias in the study. RESULTS A total of 5 RCTs involving 2 797 patients and encompassing 6 treatment regimens were ultimately included. In the assessment of overall survival， there was a trend towards survival benefit for trastuzumab combined with chemotherapy （Tra_chemo）， pertuzumab combined with trastuzumab and chemotherapy （Per_Tra_chemo）， high-dose trastuzumab combined with chemotherapy （TraHD_chemo）， lapatinib combined with chemotherapy （Lap_chemo）， and pembrolizumab combined with trastuzumab and chemotherapy （Pem_Tra_chemo） compared to chemotherapy alone （chemo）； however， the differences were not statistically significant （P＞0.05）； the top two treatment regimens in terms of the surface under the cumulative ranking curve （SUCRA） were Pem_Tra_chemo （77.8%） and TraHD_chemo （74.2%）. For progression-free survival， there was statistical significance between Per_Tra_chemo and chemo， Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Per_Tra_chemo （83.0%） and Pem_Tra_chemo （82.8%）. Regarding objective response rate， there was statistical significance between Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Pem_Tra_chemo（87.4%）and Per_Tra_chemo（72.2%）. In terms of safety， there was statistical significance in the incidence of any level of adverse events between Lap_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were chemo（87.1%）and Pem_Tra_chemo（53.8%）. Lap_chemo exhibited a higher incidence of grade ≥3 adverse events compared to chemo， and Per_Tra_chemo showed a higher incidence compared to Tra_chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Tra_chemo （79.0%） and chemo （77.6%）. CONCLUSIONS In the first-line treatment of HER2-positive advanced gastric cancer， Pem_Tra_chemo and Per_Tra_chemo regimens have relatively good efficacy， but the safety risks are relatively high， requiring close attention and whole- process management.