Economic Evaluation of Toripalimab Plus Bevacizumab Versus Sorafenib as First-Line Therapy for advanced hepatocellular carcinoma in China

Economic Evaluation of Toripalimab Plus Bevacizumab Versus Sorafenib as First-Line Therapy for advanced hepatocellular carcinoma in China | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 6 June 2025 V1 Latest version Share on Economic Evaluation of Toripalimab Plus Bevacizumab Versus Sorafenib as First-Line Therapy for advanced hepatocellular carcinoma in China Authors : Rui Fang 0000-0001-7724-2348 , feifeng sheng , tieqiao wang , and Jiajun Liang [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174919531.10670171/v1 459 views 234 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background The HEPATORCH trial demonstrated that first-line toripalimab plus bevacizumab (TPB) improves clinical efficacy in patients with unresectable hepatocellular carcinoma (HCC), however its economic implications remain unclear. This study was aimed to assess the cost-effectiveness of TPB compared with sorafenib from the perspective of the Chinese healthcare system. Methods A partitioned survival model was constructed to simulate the long-term economic outcomes for advanced HCC patients. Survival data were derived from the HEPATORCH trial using parametric curve fitting. Direct medical costs and utility values were obtained from local public healthcare databases and literature. The primary outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) evaluated against China’s willingness-to-pay (WTP) threshold. Model robustness was assessed through one-way sensitivity and probabilistic sensitivity analysis (PSA). Results In the base-case analysis, TPB resulted in an incremental cost of $15,850 and an incremental effectiveness of 0.28 QALYs, leading to an ICER of $57374.33 per QALY, higher than the predefined WTP threshold of $40,334.05 per QALY. Sensitivity analyses identified the duration of treatment bevacizumab(cycle) and cost of bevacizumab per 100 mg as key drivers of model uncertainty. The scenario analysis revealed the varying prices can influence model outcomes and ICER. Conclusion The findings from the analysis suggest that the economic advantage of toripalimab plus bevacizumab in the first-line treatment of advanced HCC is still not achieved in China. Reducing the prices of toripalimab and bevacizumab may improve the cost-effectiveness. Economic Evaluation of Toripalimab Plus Bevacizumab Versus Sorafenib as First-Line Therapy for advanced hepatocellular carcinoma in China A short running title Economic Evaluation of TPB for advanced HCC Rui Fang 1 , Tieqiao Wang 1 , Feifeng Sheng 1 , Jiajun Liang 2 , † 1 Department of Pharmacy, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China 2 Information Center, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China † Correspondence Address correspondence to: Jiajun Liang, Information Center, Guangdong Women and Children Hospital, Department of Pharmacy, Guangdong Women and Children Hospital, 541 Xingnan Avenue, Panyu, Guangzhou, Guangdong 511442, P.R.China Email: [email protected] Word count, table count, figure count The manuscript contains 2174 words (excluding the abstract and references), 4 tables and 4 figures. Keywords cost-effectiveness analysis, partitioned survival model, toripalimab plus bevacizumab, unresectable hepatocellular carcinoma What is already known about this subject: • HCC is a global health burden and major epidemiological challenge in China, with most patients diagnosed at advanced stages. • ICIs combination strategies have revolutionized the therapeutic landscape for advanced HCC and have inconsistent cost-benefit findings. • TPB’s efficacy is proven in the HEPATORCH trial and its economic implications remain unaddressed. What this study adds: First evaluates TPB’s cost-effectiveness as first-line treatment for advanced HCC in China, informing health policy and treatment strategies. Highlight the potential impact of price reductions on the cost-effectiveness of TPB, offering insights for future negotiations and healthcare resource allocation. Abstract Background The HEPATORCH trial demonstrated that first-line toripalimab plus bevacizumab (TPB) improves clinical efficacy in patients with unresectable hepatocellular carcinoma (HCC), however its economic implications remain unclear. This study was aimed to assess the cost-effectiveness of TPB compared with sorafenib from the perspective of the Chinese healthcare system. Methods A partitioned survival model was constructed to simulate the long-term economic outcomes for advanced HCC patients. Survival data were derived from the HEPATORCH trial using parametric curve fitting. Direct medical costs and utility values were obtained from local public healthcare databases and literature. The primary outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) evaluated against China’s willingness-to-pay (WTP) threshold. Model robustness was assessed through one-way sensitivity and probabilistic sensitivity analysis (PSA). Results In the base-case analysis, TPB resulted in an incremental cost of $15,850 and an incremental effectiveness of 0.28 QALYs, leading to an ICER of $57374.33 per QALY, higher than the predefined WTP threshold of $40,334.05 per QALY. Sensitivity analyses identified the duration of treatment bevacizumab(cycle) and cost of bevacizumab per 100 mg as key drivers of model uncertainty. The scenario analysis revealed the varying prices can influence model outcomes and ICER. Conclusion The findings from the analysis suggest that the economic advantage of toripalimab plus bevacizumab in the first-line treatment of advanced HCC is still not achieved in China. Reducing the prices of toripalimab and bevacizumab may improve the cost-effectiveness. 1 Introduction Hepatocellular carcinoma (HCC), a major global health burden，is the third most prevalent cause of cancer mortality worldwide (1). In China, it represents a significant epidemiological challenge, ranking as the fourth most prevalent cancer and the second leading cause of cancer-related death (2). Despite advances in early detection, 60%-70% of patients are diagnosed with advanced disease, rendering curative interventions such as surgical resection, ablation, or transplantation infeasible (3). For over a decade, the tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib have established the first-line treatment, modestly extending median overall survival (OS) to 10-15 months (4, 5). However, these advances remain insufficient, with the 5-year survival rate for advanced HCC remain poor. The emergence of immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 inhibitors (e.g., toripalimab, nivolumab, pembrolizumab, sintilimab, penpulimab, has revolutionized the therapeutic landscape for unresectable HCC by significantly improving OS (6). While single-agent ICIs failed to demonstrate OS superiority over sorafenib (7), combination strategies have emerged as a focal point of research, notably including atezolizumab plus bevacizumab (IMbrave150), cabozantinib plus atezolizumab, sintilimab plus IBI305 (ORIENT-32), camreli­zumab plus rivoceranib (CARES-310), pembrolizumab plus len­vatinib (LEAP-002), and durvalumab plus tremelimumab (HIMALAYA), Anlotinib Plus Penpulimab (APOLLO) (8-16). Several pharmacoeconomic studies have already explored the use of ICIs based combination therapies as a first-line treatment for advanced HCC. Among these, nearly twelve studies have specifically focused on cost-effectiveness analyses of ICIs plus bevacizumab or its biosimilar. However, the findings from these analyses were inconsistent, which may be related to the use of different ICIs (17-27). The HEPATORCH trial, a randomized open-label phase 3 study, demonstrated the novel combination of toripalimab with bevacizumab prolonged progression-free survival (PFS) compared with sorafenib (median 5.8 months [95% CI 4.6-7.2] vs 4.0 months [2.8-4.2]; hazard ratio [HR] 0.69 [95% CI 0.53-0.91; p=0.0086) and significantly improved OS compared with sorafenib (median 20.0 months [95% CI 15.3-23.4] vs 14.5 months [11.4-18.8]; HR 0.76 [95% CI 0.58-0.99; p=0.039). Grade 3 or higher adverse events (AEs) occurred in 102 (63%) patients in the TPB group compared with 100 (61%) in the sorafenib group, and led to discontinuation of treatment in 21 (13.0%) participants in the TPB group and 20 (12%) participants in the sorafenib group. These findings highlight its potential as a promising first-line option for advanced HCC (28). Despite its clinical efficacy, the economic implications of TPB remain unaddressed and no cost-effectiveness analyses has assessed this regimen for advanced HCC in China. This study aims to assess the cost-effectiveness of TPB versus sorafenib from the Chinese healthcare system perspective, providing essential evidence to inform value-based treatment guidelines and health policy decisions. Our study adhered to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines for reporting economic evaluations (29). 2 Methods 2.1 Model Overview A three-state partitioned survival model (PSM) was constructed using TreeAge Pro 2022(TreeAge, Williamstown, MA, USA) to compare the cost-effectiveness of TPB versus sorafenib in advanced HCC (Fig. 1) . The model consisted of three mutually exclusive health states: PFS, progressive disease (PD), and death. The model cycle was set 21 days, aligning to the therapeutic regimens in pivotal trials, with a 10-year simulation time horizon, reflecting the poor 5-year OS rate 20% of advanced HCC in China (30). 2.2 Clinical Data Inputs Individual patient survival data were digitized from Kaplan-Meier curves in the HEPATORCH trial using GetData Graph Digitizer (version 2.26) and reconstructed in R (version 4.5.0, Vienna, Austria). Six parametric models were fitted and extrapolated survival curves beyond trial follow-up period. Model selection was guided by a combination visual inspection and minimum statistical criteria of the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), with the log-normal distribution demonstrated optimal fit for simulating the survival curves. (Supplementary Table S1; Supplementary Figure S1–2). Key clinical parameters are summarized in Table 1 . 2.3 Cost and Utility Inputs Direct medical costs included medication, management of serious adverse events (SAEs), follow-up, subsequent therapy, and best supportive care. Drug prices were obtained from the China Data Platform and Guangdong Public Resources Trading Service Platform (2025) (31, 32), based on treatment duration, subsequent therapy and dosing detail (Supplementary Table S2). For SAE management, Grade ≥3 AEs with an incidence of ≥5% in HEPATORCH were included, such as hypertension, platelet count decreased, anemia, aspartate aminotransferase concentrations increased, diarrhea and palmar-plantar erythrodysesthesia syndrome (PPES), with AE management costs referenced from literature (20, 33, 34). All costs were converted to 2024 USD (1 USD = 7.1217 RMB) and adjusted for inflation via the Consumer Price Index (35). Health-related quality of life was quantified using utility values (0 = death, 1 = perfect health). Due to lack quality-of-life （QOL）data in HEPATORCH, utility values for PFS and PD (0.76 and 0.68, respectively) were adapted from literature(34). According to the Chinese Pharmacoeconomic Guidelines (2020) and WHO standards (36, 37), all inputs were discounted at 3%. The three times China’s per capita gross domestic product (GDP) in 2024 ($40334.05) was set as the willingness-to-pay (WTP) threshold (38). 2.4 Sensitivity Analysis Model robustness was evaluated through one-way sensitivity analysis PSA. In the one-way sensitivity analysis, all input parameters were varied based on ±20% change from the base-case value ( Table 1 ). For the PSA, 1,000 Monte Carlo simulations were conducted to account for parameter variability, with key model parameters sampled from predefined statistical distributions. A gamma distribution was selected for the cost parameters, and a beta distribution for probability, proportion, and preference value parameters. Cost-effectiveness acceptability curves (CEACs) and probabilistic scatter plot were generated to visualize the probability of the intervention being cost-effective across WTP thresholds. 2.5 Scenario analysis In drug pricing and economic evaluation, the varying prices can influence model outcomes and ICER. Since the inclusion of toripalimab and bevacizumab in the China National Reimbursement Drug List (NRDL), their prices have been substantially reduced, particularly when new therapeutic indications are approved. This study conducted scenario analyses to assess the impact of different price discounts within China’s healthcare framework. Specifically, we evaluated the cost-effectiveness of the TPB using pre-NRDL prices to better understand the potential financial implications of such negotiations, particularly the significant price reductions from health insurance negotiations for new indications. 3 Results 3.1 Base-case analysis The base-case analysis results with a 10-year lifetime horizon are presented in Table 2 . The total direct medical cost for TPB was $31,077 for the TPB, while sorafenib was $15,227. After adjusting for health-state utilities, TPB yielded 1.40 QALYs versus 1.12 QALYs for sorafenib, representing an incremental effectiveness of 0.28 QALYs. The ICER was $57,374.33/QALY, which above the WTP threshold of $40,334.05/QALY, revealing the TPB may not be cost-effectiveness from Chinese healthcare system. 3.2 Sensitivity Analyses The one-way sensitivity analysis results, visualized in a tornado diagram in Figure 2 , identified how the parameters values affected the ICER. The most influential variables were the duration of treatment bevacizumab(cycle) and the cost of bevacizumab per 100 mg. Although altered these parameters could resulted substantial ICER changes, $46818.66-$66294.66/QALY and $48593.64-$66155.02/QALY, respectively, they were still below the WTP. Other considerably influential factors included the utility of PD，discount rate，the utility of PFS，duration of treatment sorafenib(cycle)，cost of toripalimab per 240mg，cost of Sorafenib per200 mg，and cost of laboratory tests and imaging examination per cycle. Nevertheless, none of the variables could reduce the ICERs below the thresholds. The PSA results were presented via a cost-effectiveness acceptability curve and scatter plot in Figure 3 and Figure 4 . The scatter plot showed that most ICER scatter points were predominantly above the line of WTP thresholds of $40,334.05, indicating TPB may not a cost-effective first-line strategy. 3.3 Scenario analysis As presented in Table 4 , the pre-listing prices of toripalimab ($345.42/240 mg) plus bevacizumab ($190.97/100 mg) in China substantially exceeded the threshold of three times the 2024 Chinese GDP per capita. A 40% price reduction lowered the ICER to $36,689.10 per QALY, just below the WTP threshold. A 90% price reduction further decreased the ICER to $10,834.34 per QALY, falling below China’s GDP per capita threshold ($13,444.68). This ICER is notably lower than the $211,175.92 per QALY observed with TPB at the post-NRDL prices of toripalimab ($103.63/240 mg) plus bevacizumab ($57.29/100 mg) in China. The probability of TPB being cost effective in China was100%, 99.1%, and 63.1% at WTP thresholds of three times, 1.5 times, and one times the 2024 Chinese GDP per capita, respectively. 4 Discussion Hepatocellular carcinoma (HCC) is a highly prevalent and aggressive malignancy, imposing a significant health burden, particularly in advanced stages where curative options are limited for most patients (39, 40). In recent years, the treatment landscape has undergone transformative shifts with tyrosine kinase inhibitors like sorafenib and lenvatinib, immune checkpoint inhibitors, and most recently, multi-pathway combination therapies (6, 41, 42). Recently, the HEPATORCH trial, a randomized, open-label, phase 3 study, confirmed the TPB can prolonged progression-free survival and significantly improved overall survival compared with sorafenib, which provided a novel first-line treatment option for patients with advanced HCC. However, the price of ICI-based combinations is usually high, which may raise complex cost-benefit considerations that vary significantly across different healthcare systems. Hence, it is important to evaluate the effect of ICI-based combinations from the perspective of Pharmacoeconomics. By retrieving literature, we reviewed twenty-eight pharmacoeconomic studies on combination therapies as a first-line treatment for advanced HCC (Supplementary Table S3). After excluding network meta-analyses, system reviews, and real-world analyses, we identified 18 relevant studies. Ten evaluated atezolizumab plus bevacizumab for advanced HCC across various healthcare systems, including the US, France, Thailand, Singapore, and China (17-25). In Chinese mainland, two analyses showed were not cost-effective, with the incremental costs, incremental effectiveness, and ICERs varied widely were $156209 and $ 77139.49, 0.53, $ 322500 and $ 145546.21 respectively. This was mainly due to the high price of atezolizumab plus bevacizumab and the relatively low incremental QALY values. Two studies found sintilimab plus bevacizumab or its biosimilar cost-effective, and the incremental cost, incremental effectiveness and the ICERs were $10472 and $12065, 0.500 and 0.493, $20968/QALY and $24462/QALY respectively (26, 27). This may relate to the different duration of sintilimab and toripalimab, five cycles verse nine cycles. In summary, the pharmacoeconomic studies on ICI plus bevacizumab show inconsistent outcomes. It is essential to develop pharmacoeconomic data on novel therapeutic options for patients with advanced HCC. In the HEPATORCH trial, TPB demonstrated remarkable efficacy and safety in patients with advanced HCC. However, no studies have investigated the economic implications of TPB as a first-line treatment for advanced HCC and our study is the first cost-effectiveness analysis to explored these from the perspective of China’s healthcare system. The result revealed that TPB may not be cost-effective, with an ICER of $57,374.33 per QALY, exceeding the WTP threshold of $40,334.05 per QALY. This is similar to the previous analysis on the atezolizumab-bevacizumab from the Chinese healthcare perspective. The one-way sensitivity analysis showed that two variables mostly influenced the ICERs were duration of treatment bevacizumab(cycle) and cost of bevacizumab(100mg). Moreover, altering any parameters in the model did not change the conclusion, demonstrating the robustness of our model. Based on our cost-effective outcomes, a preliminary conclusion can be drawn that the TPB might not be more cost-effectiveness versus the sorafenib from the Chinese healthcare perspective. Scenario analyses were performed to assess the impact of incremental price reductions on cost-effectiveness, calculating ICERs for each 10% price reduction applied to the pre-NRDL prices of TPB. Using the original pricing, the ICER exceeded the WTP threshold significantly. Cost-effectiveness was achieved when the prices of TPB decreased by over 40%. Since 2017, although many novel anticancer drugs have been added in the NRDL with substantial price reductions, including TPB, their new therapeutic indication for advanced HCC are unapproved and unincluded. This analysis has several limitations. First, like many cost-effectiveness studies, this analysis also relies on clinical trial data with strict eligibility criteria, which may limit the findings’ generalizability to broader HCC populations. Second, the absence of QOL data in the HEPATORCH trial necessitates using utility values from other studies, which may not fully capture health-state preferences specific to this regimen and could affect QALY reliability. Third, our model only included SAEs with an incidence of ≥5%, which may slightly underestimate total management costs, warranting caution in resource allocation. Fourth, using validated methods for extrapolating survival from Kaplan–Meier curves may result uncertainties about post-trial outcomes persist, possibly diverging from real-world scenarios. Lastly, we did not account for broader socioeconomic factors like indirect costs or out-of-pocket expenses, and slight variations in cost data from different sources might affect the conclusions. Future studies should focus on real-world validation of quality-of-life metrics, long-term survival outcomes, and socioeconomic barriers to optimize implementation strategies and enhance model accuracy for equitable policy decisions. 5 Conclusion In conclusion, TPB is unlikely to be a cost-effective option compared with sorafenib for first-line advanced HCC treatment from the perspective of Chinese payers. However, if the price decreases as new advanced HCC therapeutic indications are added to the NRDL, TPB might become cost-effective. There were several limitations with our study, future real - world studies are needed to verify the efficacy, safety, and economics of these findings. Acknowledgements None Conflict of Interest Statement The authors declare no conflict of interest. Funding No funding was received for the research, authorship, and/or publication of this article. Data availability statement The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author. Ethical statement This economic analysis was based on a literature review and modeling techniques, and did not require approval from an Institutional Research Ethics Board. References 1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. 2. Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4(1):47-53. 3. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345-62. 4. Chen QF, Wu PH, Huang T, Shen LJ, Huang ZL, Li W. Efficacy of treatment regimens for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98(40):e17460. 5. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-73. 6. Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19(3):151-72. 7. Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77-90. 8. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-905. 9. Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023;79(2):506-15. 10. Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021;22(7):977-90. 11. Xia Y, Tang W, Qian X, Li X, Cheng F, Wang K, et al. Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial. J Immunother Cancer. 2022;10(4). 12. Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, et al. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(8):995-1008. 13. Sangro B, Chan SL, Kelley RK, Lau G, Kudo M, Sukeepaisarnjaroen W, et al. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35(5):448-57. 14. Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Hum Vaccin Immunother. 2016;12(11):2777-89. 15. Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, et al. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018;11(1):120. 16. Zhou J, Bai L, Luo J, Bai Y, Pan Y, Yang X, et al. Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial. Lancet Oncol. 2025. 17. Su D, Wu B, Shi L. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma. JAMA Netw Open. 2021;4(2):e210037. 18. Zhang X, Wang J, Shi J, Jia X, Dang S, Wang W. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma. JAMA Netw Open. 2021;4(4):e214846. 19. Gaugain L, Cawston H, Dubois de Gennes C, Sanchez Alvares J, Nahon P, Mazaleyrat B, et al. Cost-utility analysis of atezolizumab with bevacizumab in untreated unresectable or advanced hepatocellular carcinoma in France. PLoS One. 2023;18(1):e0280442. 20. Chiang CL, Chan SK, Lee SF, Choi HC. First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. Cancers (Basel). 2021;13(5). 21. Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022;128(22):3995-4003. 22. Wen F, Zheng H, Zhang P, Liao W, Zhou K, Li Q. Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states. Liver Int. 2021;41(5):1097-104. 23. Sriphoosanaphan S, Pantumongkol W, Kulpeng W, Charonpongsuntorn C, Tanwandee T, Sukeepaisarnjaroen W, et al. Cost-utility analysis of atezolizumab combined with bevacizumab for unresectable hepatocellular carcinoma in Thailand. PLoS One. 2024;19(3):e0300327. 24. Chee CE, Khara JS, Cheong J, Fong J, Sivanesan S, Choy JY, et al. Cost-effectiveness analysis of atezolizumab plus bevacizumab compared with sorafenib as first-line treatment in advanced hepatocellular carcinoma in Singapore. Expert Rev Pharmacoecon Outcomes Res. 2024;24(5):631-41. 25. Tseng CY, Tsai YW, Shiu MN. Cost-effectiveness analysis of atezolizumab plus bevacizumab versus sorafenib in first line treatment for Chinese subpopulation with unresectable hepatocellular carcinoma. Front Oncol. 2023;13:1264417. 26. Zhou T, Cao Y, Wang X, Yang L, Wang Z, Ma A, et al. Economic Evaluation of Sintilimab Plus Bevacizumab Versus Sorafenib as a First-line Treatment for Unresectable Hepatocellular Carcinoma. Adv Ther. 2022;39(5):2165-77. 27. Zhou T, Wang X, Cao Y, Yang L, Wang Z, Ma A, et al. Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma. BMC Health Serv Res. 2022;22(1):1367. 28. Shi Y, Han G, Zhou J, Shi X, Jia W, Cheng Y, et al. Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial. Lancet Gastroenterol Hepatol. 2025. 29. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C, et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) Statement: Updated Reporting Guidance for Health Economic Evaluations. Value Health. 2022;25(1):3-9. 30. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023-75. 31. Guangzhou. Gprtspppi. PLATFORM GPRTS. https://gpogzggzycn/. 2025. 32. (2025) Y. Drug Pice. Available at: https://www.yaozh.com/ (Accessed May, 2025). 2025. 33. You M, Luo L, Lu T, Chen S, He Y. Cost-effectiveness analysis of benmelstobart, anlotinib, and chemotherapy in extensive-stage small-cell lung cancer. Front Immunol. 2024;15:1477146. 34. Sun Y, Xu K, Yao H, Wei J, Ding B, Qian X, et al. Cost-effectiveness of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a comparative analysis in China, the United States and Europe. Int J Clin Pharm. 2025;47(1):196-209. 35. 2024. BOC. Foreign exchange rate. https://wwwboccn/sourcedb/whpj/. 2024. 36. Murray CJ, Evans DB, Acharya A, Baltussen RM. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235-51. 37. Association. CP. Chinese Pharmacoeconomic Evaluation Guidelines (2020). https:// www cpa org cn/ cpadmn/attac hed/ file/ 20201 203/ 16069 77380 634185 pdf. 2020; Accessed 01 Mar 2024. 38. NBoso. C. Statistical Bulletin of National Economic and Social Development of the People’s Republic of China in 2021. Available online at https://wwwstatsgovcn/xxgk/gknb/tjj_gknb/202501/t20250126_1958450html 2024;(accessed Feb, 2025). 39. Rumgay H, Ferlay J, de Martel C, Georges D, Ibrahim AS, Zheng R, et al. Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer. 2022;161:108-18. 40. Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv Cancer Res. 2021;149:1-61. 41. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-90. 42. Zhu AX, Chabner BA, Tanabe KK. New trends and novel treatment for hepatocellular carcinoma: a global perspective. Oncologist. 2010;15 Suppl 4:1-4. 43. He Y, Lin W, Cai Z, Huang Y, You M, Lei M, et al. Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma. Front Pharmacol. 2023;14:1219694. 44. Wang L, Lv N, Gao Y, Yan C, Huo X, Diao R. Cost-effectiveness analysis of penpulimab combined with paclitaxel and carboplatin as a first-line treatment for metastatic squamous non-small cell lung cancer in China. BMJ Open. 2025;15(3):e091650. 45. Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, et al. Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016;316(10):1093-103. Table 1 Log-normal survival model parameters for PFS and OS. Low Up Survival model for TPB Log-normal model for PFS meanlog =1.761 0.093 1.579 1.944 sdlog =1.048 0.079 0.905 1.214 Log-normal model for OS meanlog =2.952 0.096 2.764 3.141 sdlog =1.110 0.083 0.959 1.284 Survival model for Sorafenib Log-normal model for PFS meanlog =1.397 0.074 1.253 1.541 sdlog =0.852 0.058 0.745 0.975 Log-normal model for OS meanlog =2.707 0.085 2.541 2.872 sdlog =1.035 0.069 0.909 1.179 TPB, Toripalimab plus Bevacizumab; PFS, progression-free survival; OS, overall survival. Table 2 Key clinical and health preference data Minimum Maximum Costs ($) Toripalimab (240mg) 345.42 276.34 414.51 Gamma Local charge Bevacizumab (100mg) 190.97 152.77 229.16 Gamma Local charge Sorafenib (200 mg) 6.32 5.06 7.58 Gamma Local charge Administration cost 127.40 101.92 152.88 Gamma Local charge Cost of hospitalization and daily care 47.32 37.85 56.78 Gamma Local charge Cost of Laboratory tests and Imaging examination per cycle 672.02 537.62 806.42 Gamma Local charge Subsequent anti-cancer therapy in sorafenib group per cycle ($) 163.70 130.96 196.44 Gamma Local charge Subsequent anti-cancer therapy in TPB group per cycle ($) 142.23 113.78 170.67 Gamma Local charge Routine follow-up cost 73.57 58.86 88.28 Gamma Local charge Best supportive care per cycle ($) 274.00 219.20 328.80 Gamma Local charge End-of-life care 1460.30 1168.24 1752.36 Gamma (33) Costs of SAEs ($) Hypertension 0.17 0.14 0.21 Gamma (34) Platelet count decreased 1640.63 1312.50 1968.75 Gamma (34) Anemia 152.48 121.98 182.98 Gamma (34) AST increased 33.31 26.65 39.97 Gamma (43) Diarrhea 3.019 2.42 3.62 Gamma (44) PPES 145.65 116.52 174.78 Gamma (44) Risk of SAEs in Anlotinib plus Penpulimab group（%） Hypertension 0.160 0.13 0.19 Beta (28) Thrombocytopenia 0.100 0.08 0.12 Beta (28) Anemia 0.060 0.05 0.07 Beta (28) AST increased 0.030 0.02 0.04 Beta (28) Diarrhea 0.010 0.01 0.01 Beta (28) PPES 0.000 0.00 0.00 Beta (28) Risk of SAEs in sorafenib group（%） Hypertension 0.120 0.10 0.14 Beta (28) Thrombocytopenia 0.030 0.02 0.04 Beta (28) Anemia 0.040 0.03 0.05 Beta (28) AST increased 0.060 0.05 0.07 Beta (28) Diarrhea 0.070 0.06 0.08 Beta (28) PPES 0.100 0.08 0.12 Beta (28) Utility value and Discount rate PFS 0.68 0.544 0.816 Beta (34) PD 0.42 0.336 0.504 Beta (34) Discount rate 0.03 0 0.08 Fixed (45) TPB, Toripalimab plus Bevacizumab; SAEs, serious adverse events; AST: Aspartate aminotransferase; PPES, Palmar-planta erythrodysesthesia syndrome; PFS, progression-free survival; PD, progressive disease. Table 3 Summary of cost and outcome results of the cost-effectiveness analysis TPB 31076.56 1.40 15849.59 0.28 57374.33 Sorafenib 15226.97 1.12 TPB, Toripalimab plus Bevacizumab; QALY, quality-adjusted life year; ICER, Incremental cost-effectiveness ratio. Table 4 Results of scenario analysis 10% 57374.33 20% 52202.51 30% 41861.15 40% 36689.1 50% 34640.67 60% 26347.75 70% 211175.92 80% 16003.87 90% 10834.34 TPB, toripalimab plus bevacizumab, ICER, incremental cost-effectiveness ratio. Figure 1 Model Structure of the PSM with three health states. (A) Decision Tree used to compare the standard first-line treatment for patients with advanced HCC. (B) The PSM model simulated three health states: progression-free survival, progressive disease and death. TPB, toripalimab plus bevacizumab; HCC, hepatocellular carcinoma; PSM, partitioned survival model. Figure 2 Tornado diagram summarized the result of one-way sensitivity analysis. TPB, toripalimab plus bevacizumab; ICER, incremental cost-effectiveness ratios; EV, expected value; PFS, progression-free survival; PD, progressive disease. Figure 3 Cost-effectiveness Acceptability Curves for TPB versus Sorafenib. The light blue dash lines indicate the threshold of willingness-to-pay. TPB, toripalimab plus bevacizumab; WTP, willingness-to-pay. Figure 4 Scatter plot of the probabilistic sensitivity analysis for TPB versus Sorafenib. The black dash lines indicate the threshold of willingness-to-pay. TPB, toripalimab plus bevacizumab; WTP, willingness-to-pay. Information & Authors Information Version history V1 Version 1 06 June 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords gastroenterology health services research hepatology immunology immunotherapy pharmacoeconomics Authors Affiliations Rui Fang 0000-0001-7724-2348 View all articles by this author feifeng sheng View all articles by this author tieqiao wang View all articles by this author Jiajun Liang [email protected] View all articles by this author Metrics & Citations Metrics Article Usage 459 views 234 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Rui Fang, feifeng sheng, tieqiao wang, et al. Economic Evaluation of Toripalimab Plus Bevacizumab Versus Sorafenib as First-Line Therapy for advanced hepatocellular carcinoma in China. Authorea . 06 June 2025. DOI: https://doi.org/10.22541/au.174919531.10670171/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174919531.10670171/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9fee5db16fcc1b23',t:'MTc3OTMxMTgyMw=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();