目的:肝细胞癌(HCC)是全世界癌症相关死亡的主要原因之一,特别是在中国,带来了沉重的社会经济负担。几种免疫组合疗法在不可切除的HCC的一线治疗中显示出有希望的疗效,并在临床实践中广泛使用。然而,哪种组合是最实惠的,目前尚不清楚。我们的研究从中国付款人的角度评估了免疫组合作为不可切除的HCC患者的一线治疗的成本效益。
方法:根据五个多中心建立马尔可夫模型,第三阶段,开放标签,随机试验(喜马拉雅,IMbrave150,ORIENT-32,CARES-310,LEAP-002)调查曲美木单抗加杜瓦单抗(STRIDE)的成本效益,阿替珠单抗加贝伐单抗(A+B),sintilimab加贝伐单抗生物仿制药(IBI305)(S+B),camrelizumab加rivoceranib(C+R),和派博利珠单抗加乐伐替尼(P+L)。包括三种疾病状态:无进展生存期(PFS),进行性疾病(PD)以及死亡。从华西医院搜索医疗费用,出版文献或红皮书。评估了成本效益比(CER)和增量成本效益比(ICER),以比较不同组合之间的成本。进行敏感性分析以评估模型的鲁棒性。
结果:C+R的总成本和质量调整寿命年(QALYs),S+B,P+L,A+B和STRIDE分别为$12,109.27和0.91,$26,961.60和1.12,$55,382.53和0.83,$70,985.06和0.90,$84,589.01和0.73,导致C+R最具成本效益的策略,CER为每QALY13,306.89美元,其次是S+B,CER为每QALY24,072.86美元。与C+R相比,S+B策略的ICER为每QALY70,725.38美元,当愿意支付门槛超过73,500美元/质量时,这将成为最具成本效益的。在亚组分析中,随着亚洲结果在Leap-002试验中的应用,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一线全身治疗的有希望的免疫组合疗法之一,camrelizumab+rivoceranib被证明是最具成本效益的战略,这需要进一步的研究,以最好地告知现实世界的临床实践。
OBJECTIVE: 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.
CONCLUSIONS: 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.