Table_1_A global analysis of the value of precision medicine in oncology – The case of non-small cell lung cancer.DOCX

ObjectivesBiomarker testing is indispensable for the implementation of precision medicine (PM) in oncology. The aim of this study was to assess the value of biomarker testing from a holistic perspective based on the example of advanced non-small cell lung cancer (aNSCLC).
Materials and methodsA partitioned survival model was populated with data from pivotal clinical trials of first-line treatments in aNSCLC. Three testing scenarios were considered; “no biomarker testing” encompassing chemotherapy treatment, “sequential testing” for EGFR and ALK encompassing treatment with targeted- or chemotherapy, and “multigene testing” covering EGFR, ALK, ROS1, BRAF, NTRK, MET, RET and encompassing treatment with targeted- or immuno(chemo)therapy. Analyses of health outcomes and costs were run for nine countries (Australia, Brazil, China, Germany, Japan, Poland, South Africa, Turkey, United States). A 1-year and 5-year time horizon was applied. Information on test accuracy was combined with country-specific information on epidemiology and unit costs.
ResultsCompared to the no-testing scenario, survival improved and treatment-related adverse events decreased with increased testing. Five-year survival increased from 2% to 5–7% and to 13–19% with sequential testing and multigene testing, respectively. The highest survival gains were observed in East Asia due to a higher local prevalence of targetable mutations. Overall costs increased with increased testing in all countries. Although costs for testing and medicines increased, costs for treatment of adverse events and end-of-life care decreased throughout all years. Non-health care costs (sick leave and disability pension payments) decreased during the first year but increased over a 5-year horizon.
ConclusionThe broad use of biomarker testing and PM in aNSCLC leads to more efficient treatment assignment and improves health outcomes for patients globally, in particular prolonged progression-free disease phase and overall survival. These health gains require investment in biomarker testing and medicines. While costs for testing and medicines would initially increase, cost decreases for other medical services and non-health care costs may partly offset the cost increases.

研究目的：生物标志物检测（biomarker testing）是肿瘤学（oncology）中实施精准医学（precision medicine, PM）不可或缺的核心环节。本研究以晚期非小细胞肺癌（advanced non-small cell lung cancer, aNSCLC）为研究实例，旨在从全局视角评估生物标志物检测的应用价值。

材料与方法：本研究采用分区生存模型（partitioned survival model），基于晚期非小细胞肺癌一线治疗的关键临床试验（pivotal clinical trials）数据进行参数填充。共设置三类检测场景：「无生物标志物检测」场景，即采用化疗方案；「序贯检测（sequential testing）」场景，针对表皮生长因子受体（EGFR）与间变性淋巴瘤激酶（ALK）开展检测，后续匹配靶向治疗或化疗方案；「多基因检测（multigene testing）」场景，覆盖EGFR、ALK、ROS1、BRAF、NTRK、MET、RET等靶点，后续匹配靶向治疗或免疫（化学）治疗方案。研究针对澳大利亚、巴西、中国、德国、日本、波兰、南非、土耳其、美国共9个国家，开展健康结局与医疗成本分析，分析时限设定为1年与5年。本研究将检测准确性相关数据与各国特异性流行病学数据、单位成本数据进行整合。

结果：相较于无检测场景，随着检测覆盖范围扩大，患者生存期得以延长，治疗相关不良事件发生率降低。相较于无检测场景，序贯检测与多基因检测场景下的5年生存率分别从2%提升至5%~7%、13%~19%。由于东亚地区可靶向突变的本地患病率更高，该区域的生存获益最为显著。所有国家的医疗总成本均随检测覆盖范围扩大而升高：尽管检测与药物成本有所上升，但各年度的不良事件治疗与临终关怀成本均有所降低。非医疗成本（病假与残疾抚恤金支出）在第1年内有所下降，但在5年分析时限内呈现上升趋势。

结论：在晚期非小细胞肺癌诊疗中广泛应用生物标志物检测与精准医学，可实现更合理的治疗方案分配，改善全球患者的健康结局，尤其是延长无进展疾病阶段与总生存期（overall survival）。实现此类健康获益需投入生物标志物检测与药物相关成本。尽管检测与药物成本初始会有所上升，但其他医疗服务成本与非医疗成本的降低可部分抵消该部分成本增量。