VA Palo Alto Health Care System, Palo Alto, California.
Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University School of Medicine, Stanford, California; and.
J Natl Compr Canc Netw. 2020 Sep;18(9):1200-1209. doi: 10.6004/jnccn.2020.7563.
The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors.
We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses.
Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained.
At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.
Lanreotide 抗增殖反应的对照研究（CLARINET）试验表明，与安慰剂相比，初始接受兰瑞肽治疗的患者无进展生存期延长。我们评估了转移性肠胰神经内分泌肿瘤（NETs）患者初始使用兰瑞肽与进展后使用兰瑞肽进行主动监测的成本效益，这两种治疗方案均被 NCCN 肿瘤学临床实践指南推荐用于神经内分泌和肾上腺肿瘤。
我们开发了一个与 CLARINET 试验及其扩展相校准的马尔可夫模型。我们基于 CLARINET 安慰剂臂来制定主动监测策略。我们计算了每质量调整生命年（QALY）的增量成本效益比（ICER）。我们将兰瑞肽的成本设定为每 120mg7638 美元（平均销售价格加 6%），使用已发表的效用值（稳定疾病，0.77；进展疾病，0.61），采用医疗保健部门的观点和终生时间范围，并按每年 3%的速度贴现成本和效益。我们考察了对生存外推的敏感性，并对奥曲肽长效释放（LAR）（每 30mg6183 美元）进行了建模。我们进行了单因素、多因素和概率敏感性分析。
初始使用兰瑞肽可获得 5.21 QALYs 和 804600 美元的成本。进展后使用兰瑞肽进行主动监测可获得 4.84 QALYs 和 590200 美元的成本，ICER 为 578500 美元/QALY。将兰瑞肽的价格降低 95%（至 370 美元）或 85%（至 1128 美元）/120mg，可使初始使用兰瑞肽达到 100000 美元/QALY 或 150000 美元/QALY 的 ICER。在一系列生存曲线外推情景中，将兰瑞肽的价格设定在 370 美元至 4000 美元或 1130 美元至 5600 美元/120mg，分别可达到 100000 美元/QALY 或 150000 美元/QALY 的 ICER。我们的研究结果在广泛的敏感性分析中是稳健的。奥曲肽 LAR 的 ICER 为 482700 美元/QALY。
按照目前的价格，兰瑞肽作为转移性肠胰神经内分泌肿瘤患者的初始治疗方法并不具有成本效益，应保留用于进展后的治疗。要使初始治疗具有成本效益，兰瑞肽的价格需要降低 48%至 95%或 27%至 86%，才能达到 100000 美元/QALY 或 150000 美元/QALY 的 ICER。
