Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Syreon Research Institute, Budapest, Hungary.
Value Health. 2023 Feb;26(2):193-203. doi: 10.1016/j.jval.2022.08.006. Epub 2022 Oct 11.
This study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients.
The health economic model consisted of a decision tree reflecting the NTRK testing phase followed by a microsimulation model reflecting treatment with either entrectinib or SoC. Efficacy of entrectinib was based on data from basket trials, whereas historical data from NTRK-negative patients were corrected for the prognostic value of NTRK fusions to model SoC.
"Testing" (testing for NTRK fusions, with subsequent entrectinib treatment in NTRK-positive patients and SoC in NTRK-negative patients) had higher per-patient quality-adjusted life-years (QALYs) and costs than "No testing" (SoC for all patients), with a difference of 0.0043 and €732, respectively. This corresponded to an incremental cost-effectiveness ratio (ICER) of €169 957/QALY and, using a cost-effectiveness threshold of €80 000/QALY, an incremental net monetary benefit of -€388. When excluding the costs of genetic testing for NTRK fusions, the ICER was reduced to €36 290/QALY and the incremental net monetary benefit increased to €188.
When treatment requires the identification of a genetic marker, the associated costs and effects need to be accounted for. Because of the low prevalence of NTRK fusions, the number needed-to-test to identify patients eligible for entrectinib is large. Excluding the testing phase reduces the ICER substantially.
本研究以恩曲替尼为例，解决了几种评估非组织学依赖性治疗的挑战。非组织学依赖性治疗是基于肿瘤的遗传标志物（无论肿瘤类型如何）提供的。我们评估了对所有患者进行 NTRK 融合检测并对阳性患者用恩曲替尼进行治疗，与所有患者不进行检测和采用标准治疗（SoC）相比，其终生成本效益。
健康经济学模型由一个决策树组成，该决策树反映了 NTRK 检测阶段，随后是一个微模拟模型，反映了用恩曲替尼或 SoC 进行治疗。恩曲替尼的疗效基于篮子试验的数据，而来自 NTRK 阴性患者的历史数据则根据 NTRK 融合的预后价值进行校正，以模拟 SoC。
“检测”（对 NTRK 融合进行检测，随后对 NTRK 阳性患者用恩曲替尼治疗，对 NTRK 阴性患者用 SoC 治疗）比“不检测”（所有患者用 SoC）具有更高的每位患者质量调整生命年（QALY）和成本，差异分别为 0.0043 和 732 欧元。这对应于增量成本效益比（ICER）为 169957 欧元/QALY，使用 80000 欧元/QALY 的成本效益阈值，增量净货币收益为-388 欧元。当排除 NTRK 融合的基因检测成本时，ICER 降低至 36290 欧元/QALY，增量净货币收益增加至 188 欧元。
当治疗需要确定遗传标志物时，需要考虑相关的成本和效果。由于 NTRK 融合的患病率较低，因此需要进行大量的检测才能确定有资格接受恩曲替尼治疗的患者。排除检测阶段会大大降低 ICER。
