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不可切除肝细胞癌的一线免疫联合治疗:成本效益分析。

Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

机构信息

Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Med-X Center for Informatics, Sichuan University, Chengdu, China.

出版信息

Cancer Med. 2024 Aug;13(16):e70094. doi: 10.1002/cam4.70094.

Abstract

BACKGROUND AND AIMS

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death all over the world, and brings a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. Nevertheless, which combination is the most affordable one is unknown. Our study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the perspective of Chinese payers.

METHODS

A Markov model was built according to five multicenter, phase III, open-label, randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A + B), sintilimab plus bevacizumab biosimilar (IBI305) (S + B), camrelizumab plus rivoceranib (C + R), and pembrolizumab plus lenvatinib (P + L). Three disease states were included: progression free survival (PFS), progressive disease (PD) as well as death. Medical costs were searched from West China Hospital, published literatures or the Red Book. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model.

RESULTS

The total cost and quality-adjusted life years (QALYs) of C + R, S + B, P + L, A + B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73, respectively, resulting in the most cost-effective strategy of C + R with CER of $13,306.89 per QALY followed by S + B with CER of $24,072.86 per QALY. Compared with C + R, the ICER of S + B strategy was $70,725.38 per QALY, which would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust.

CONCLUSION

As one of the promising immuno-combination therapies in the first-line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.

摘要

背景与目的

肝细胞癌(HCC)是全球导致癌症相关死亡的主要原因之一,在中国尤其带来了沉重的社会经济负担。几种免疫联合疗法在不可切除 HCC 的一线治疗中显示出了有前景的疗效,并广泛应用于临床实践。然而,哪种联合疗法最具性价比尚不清楚。本研究从中国支付者的角度评估了不可切除 HCC 患者一线治疗中免疫联合疗法的成本效益。

方法

根据五项多中心、三期、开放标签、随机试验(Himalaya、IMbrave150、ORIENT-32、CARES-310、LEAP-002),构建了一个马尔可夫模型,以评估 tremelimumab 加 durvalumab(STRIDE)、atezolizumab 加 bevacizumab(A+B)、sintilimab 加 bevacizumab 生物类似药(IBI305)(S+B)、camrelizumab 加 rivoceranib(C+R)和 pembrolizumab 加 lenvatinib(P+L)作为不可切除 HCC 一线治疗的成本效益。该模型包含三个疾病状态:无进展生存期(PFS)、疾病进展(PD)和死亡。医疗费用从华西医院、已发表的文献或《国家医保药品目录》中检索。采用成本效益比值(CER)和增量成本效益比值(ICER)来比较不同组合之间的成本。进行敏感性分析以评估模型的稳健性。

结果

C+R、S+B、P+L、A+B 和 STRIDE 的总成本和质量调整生命年(QALYs)分别为 12,109.27 美元和 0.91、26,961.60 美元和 1.12、55,382.53 美元和 0.83、70,985.06 美元和 0.90、84,589.01 美元和 0.73,其中最具性价比的策略是 C+R,CER 为每 QALY 13,306.89 美元,其次是 S+B,CER 为每 QALY 24,072.86 美元。与 C+R 相比,S+B 策略的 ICER 为每 QALY 70,725.38 美元,当意愿支付阈值超过 73,500/QALY 时,S+B 策略将成为最具性价比的策略。在亚组分析中,采用 Leap-002 试验的亚洲结果,模型结果与全球数据相同。在敏感性分析中,随着参数的变化,结果是稳健的。

结论

作为 HCC 一线系统治疗中具有前景的免疫联合疗法之一,camrelizumab 加 rivoceranib 具有成为最具性价比策略的潜力,值得进一步研究以更好地为实际临床实践提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/092f/11327610/a8deabb9899c/CAM4-13-e70094-g005.jpg

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