Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.
Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.
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微卫星不稳定性高（MSI-H）/错配修复缺陷（dMMR）转移性结直肠癌（mCRC）患者对检查点抑制剂治疗显示出显著的反应，但这些治疗的经济影响尚不清楚。使用决策分析模型来探讨MSI-H/dMMR mCRC治疗的有效性和成本负担。在2种治疗方案中模拟MSI-H/dMMR mCRC假设患者的治疗：三线治疗和探索性一线治疗。比较的治疗为nivolumab、ipilimumab和nivolumab、曲氟尿苷和替吡嘧啶（三线治疗）以及mFOLFOX 6和西妥昔单抗（一线治疗）。疾病进展、药物毒性和生存率基于CheckMate 142，TAS-102在标准化疗难治性转移性结直肠癌患者中的研究（RECOURSE）和癌症和白血病组B/西南肿瘤组80405试验。分析的结果包括生存（生命年），质量调整生命年（QER）和增量成本效益比（ICER）。伊匹单抗联合纳武单抗是最有效的策略与纳武利尤单抗相比（三线治疗为10.69生命年和9.25 Qs;一线治疗为10.69生命年和9.44 Qs）（三线8.21生命年，6.76生命年）;一线治疗为8.21生命年和7.00 Qdos）、曲氟尿苷和替吡嘧啶（0.74生命年和0.07 Qdos）以及mFOLFOX 6和西妥昔单抗（2.72生命年和1.63 Qdos）。然而，与曲氟尿苷和替吡嘧啶（nivolumab ICER，153，000美元; ipilimumab和nivolumab ICER，162，700美元）或mFOLFOX 6和西妥昔单抗（nivolumab ICER，150，700美元; ipilimumab和nivolumab ICER，158，700美元）相比，检查点抑制剂治疗都不具有成本效益。该建模分析发现，单检查点和双检查点阻断对于MSI-H/dMMR mCRC可能比化疗更有效，但它们不具有成本效益，主要是因为药物成本。药物价格和/或维持nivolumab持续时间的降低可能使ipilimumab和nivolumab具有成本效益。应进行前瞻性临床试验，以探索维持nivolumab的最佳持续时间。
Patients with microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third-line treatment), and mFOLFOX6 and cetuximab (first-line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS-102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE) and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life-years), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life-years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life-years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost-effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI-H/dMMR mCRC than chemotherapy, but they were not cost-effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab costeffective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab.
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影响因子：
45.3
作者：
Kohn, Christine G.;Zeichner, Simon B.;Flowers, Christopher R.
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3.4
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影响因子：
10.3
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3.6
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Briggs, Andrew H.;Weinstein, Milton C.;Paltiel, A. David
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影响因子：
2.1
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Caro, J. Jaime;Nord, Erik;Kolominsky-Rabas, Peter
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