维恩妥尤联合帕博利珠单抗一线治疗既往未接受治疗的晚期尿路上皮癌的成本-效用分析

Cost-effectiveness analysis of the combination of enfortumab vedotin and pembrolizumab in first-line treatment of previously untreated advanced urothelial carcinoma

摘要

目的: 从中国卫生体系角度出发,评估维恩妥尤联合帕博利珠单抗在治疗晚期尿路上皮癌方面的经济性。方法: 基于EV-302的临床试验数据构建动态Markov模型,采用成本-效用分析进行经济性评价,并对主要参数进行单因素敏感性分析和概率敏感性分析验证基础分析结果的稳健性。结果: 研究结果显示,维恩妥尤联合帕博利珠单抗组较标准化疗组每多获得一个质量调整生命年(quality-adjusted life year,QALYs),需额外花费2 358 823.11元。单因素敏感性分析结果显示,对增量-成本效果比(incremental cost-effectiveness ratio,ICER)影响程度较大的参数是无进展状态效用值和维恩妥尤单抗成本。概率敏感性分析结果显示,维恩妥尤单抗联合帕博利珠单抗组在支付意愿阈值为我国2024年3倍人均GDP下不具有经济性。结论: 维恩妥尤单抗联合帕博利珠单抗组对比标准化疗剂组在治疗晚期尿路上皮癌上不具备经济性优势。

Abstract

Objective: From the perspective of the Chinese healthcare system, to evaluate the cost-effectiveness of enfortumab vedotin and pembrolizumab in the treatment of advanced urothelial carcinoma. Methods: A dynamic Markov model was constructed based on data from the EV-302 trial, and cost-utility analysis (CUA) was used for economic evaluation. Deterministic (one-way) sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted on main parameters to verify the robustness of the base-case analysis results. Results: The analysis showed that for every additional quality-adjusted life year (QALY) in the enfortumab vedotin plus pembrolizumab group compared to the standard chemotherapy group, an additional cost of 2 358 823.11 yuan was required. The results of the deterministic sensitivity analysis showed that the most influential factors on incremental cost-effectiveness ratio (ICER) were the utility value of the progression-free state and the cost of enfortumab vedotin. The probabilistic sensitivity analysis results indicated that the combination of enfortumab vedotin and pembrolizumab was not cost-effective at a willingness-to-pay threshold equivalent to three times China's 2024 per capita GDP. Conclusion: The combination of enfortumab vedotin and pembrolizumab does not represent a cost-effectiveness strategy compared with the standard chemotherapy group in the treatment of advanced urothelial carcinoma.

关键词

维恩妥尤单抗 / 帕博利珠单抗 / 尿路上皮癌 / 成本-效用分析 / Markov模型

Key words

enfortumab vedotin / pembrolizumab monoclonal antibody / urothelial carcinoma / cost-effectiveness analysis / markov model

[1] ROUPRÊT M, SEISEN T, BIRTLE AJ, et al. European association of urology guidelines on upper urinary tract urothelial carcinoma: 2023 update[J]. Eur Urol, 2023, 84(1): 49-64.
[2] ROVIELLO G, CATALANO M, NOBILI S, et al. Focus on biochemical and clinical predictors of response to immune checkpoint inhibitors in metastatic urothelial carcinoma: where do we stand?[J]. Int J Mol Sci, 2020, 21(21): 7935.
[3] VASSILIOU V, KATSILA T, SODERGREN SC, et al. Radiotherapy in metastatic urothelial carcinoma: rationale and clinical applications[J]. Anticancer Res, 2022, 42(8): 3767-3778.
[4] HE W, CHEN CH, LIN TX, et al. Epidemiology, treatments, and related biomarkers of locally advanced or metastatic urothelial carcinoma in Chinese population: a scoping review[J]. Cancer Med, 2023, 12(14): 15384-15403.
[5] THOMAS J, SUN M, GETZ T, et al. Antibody-drug conjugates for urothelial carcinoma[J]. Urol Oncol Semin Orig Investig, 2023, 41(10): 420-428.
[6] PANG K, SHI ZD, WEI LY, et al. Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade[J]. Drug Resist Updat, 2023, 66: 100907.
[7] O'DONNELL PH, MILOWSKY MI, PETRYLAK DP, et al. Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer[J]. J Clin Oncol, 2023, 41(25): 4107-4117.
[8] POWLES T, VALDERRAMA BP, GUPTA S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer[J]. N Engl J Med, 2024, 390(10): 875-888.
[9] POWLES T, BELLMUNT J, COMPERAT E, et al. ESMO Clinical Practice Guideline interim update on first-line therapy in advanced urothelial carcinoma[J]. Ann Oncol, 2024, 35(6): 485-490.
[10] FLAIG TW, SPIESS PE, ABERN M, et al. NCCN Guidelines Insights: Bladder Cancer, Version 3.2024[J]. J Natl Compr Canc Ne, 2024, 22(4):10.
[11] 尹瑞华, 王庆华, 郑红娟, 等. 晚期食管鳞状细胞癌一线多种PD-1抑制剂免疫治疗策略的成本-效用分析[J]. 中国肿瘤生物治疗杂志, 2023, 30(2): 150-155.
[12] 刘国恩. 中国药物经济学评价指南2020[M]. 北京: 中国市场出版社, 2020, 19(4): 27-28.
[13] DREVON D, FURSA SR, MALCOLM AL. Intercoder reliability and validity of WebPlotDigitizer in extracting graphed data[J]. Behav Modif, 2017, 41(2): 323-339.
[14] GUYOT P, ADES AE, OUWENS MJNM, et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves[J]. BMC Med Res Methodol, 2012, 12: 9.
[15] LIU N, ZHOU YH, JACK LEE J. IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves[J]. BMC Med Res Methodol, 2021, 21(1): 111.
[16] 于月玮, 武羽, 杨雪, 等. DRG付费改革背景下慢加急性肝衰竭患者住院费用的真实世界研究[J]. 中国医药导刊, 2025, 27(2): 166-170.
[17] 冯冰, 张菁, 高宁, 等. 基于中国卫生体系的呋喹替尼联合紫杉醇二线治疗晚期胃癌或胃食管结合部腺癌成本效果分析[J]. 中国药业, 2025, 34(12): 106-110.
[18] LI XY, LI WC, HOU LP. A trial-based cost-effectiveness analysis of bevacizumab and chemotherapy versus chemotherapy alone for advanced nonsquamous non-small-cell lung cancer in China[J]. Value Health Reg Issues, 2019, 18: 1-7.
[19] 苏广全, 易仁平, 方萍萍, 等. 伏美替尼对比吉非替尼单药一线治疗EGFR突变晚期非小细胞肺癌的成本效用分析[J/OL]. 医药导报, 1-12[2025-08-16].https://link.cnki.net/urlid/42.1293.R.20240122.1529.002.
[20] 胡钊, 刘永军. 阿得贝利单抗一线治疗广泛期小细胞肺癌的药物经济学评价[J]. 中国药物经济学, 2025, 20(3): 9-16.
[21] 何银梅, 李晓, 刘晓丽, 等. 戈沙妥珠单抗对比单药化疗后线治疗HR+/HER2-晚期转移性乳腺癌的成本-效用分析[J]. 中国药房, 2024, 35(20): 2493-2498.
[22] 居文祥, 赵荧荧, 路萝兰, 等. 贝伐珠单抗联合厄洛替尼一线治疗晚期EGFR突变型非鳞状NSCLC的成本-效用分析[J]. 中国药房, 2024, 35(11): 1357-1362.
[23] 严小雨, 路云, 常峰. 斯鲁利单抗联合化疗一线治疗晚期食管鳞状细胞癌的成本-效果分析[J]. 中国药房, 2023, 34(14): 1724-1729.
[24] 齐冉. 帕博利珠单抗联合化疗方案一线治疗晚期三阴性乳腺癌的药物经济学评价[D]. 石家庄: 河北医科大学, 2023.
[25] YOU MJ, ZHENG QY, HE Y. Enfortumab vedotin plus pembrolizumab as a first-line treatment for advanced urothelial carcinoma: a cost-effectiveness analysis from China based on the EV-302 trial[J]. Front Pharmacol, 2024, 15: 1412292.