PD-L1检测指导中国非小细胞肺癌患者免疫治疗的成本效果分析

doi:10.19401/j.cnki.1007-3639.2025.02.011

摘要/Abstract

摘要：

背景与目的：根据国家癌症中心最新数据显示，中国肺癌发病率和死亡率均居所有恶性肿瘤首位，且85%为非小细胞肺癌（non-small cell lung cancer，NSCLC）。近年来，以程序性死亡[蛋白]-1（programmed death-1，PD-1）/程序性死亡[蛋白]配体-1（programmed death ligand-1，PD-L1）免疫检查点抑制剂为主的免疫治疗在肺癌的治疗中取得了突破性的进展，为肺癌患者带来了更多的生存获益。本研究旨在评估使用不同PD-L1检测方案指导NSCLC患者免疫治疗的成本和效果，为中国NSCLC患者选择具有成本效果的诊断以及指导免疫单药方案提供科学依据。方法：基于卫生体系视角，构建决策树模型，模拟评估早中期（ⅡA~ⅢB期）、晚期（Ⅳ期）NSCLC患者接受Ventana SP263检测、Dako 22C3即用型及Dako 22C3浓缩液检测的成本，以及获得正确诊断且接受正确治疗的比例（正确诊治率）。通过增量分析比较SP263相对于其他检测方式的经济性。通过单因素敏感性分析和概率敏感性分析检验基础分析结果的稳健性。结果：指导NSCLC早中期患者化疗后辅助阿替利珠单抗治疗时，相比22C3即用型检测方案或22C3浓缩液检测方案，SP263检测方案每正确诊断且接受正确治疗一位患者需要的增量成本为9 449元，SP263检测方案具有成本效果。指导NSCLC晚期患者免疫单药治疗时，与22C3即用型或22C3浓缩液检测方案相比，SP263检测方案可以指导多种免疫单药治疗（阿替利珠单抗单药、帕博利珠单抗单药），同时正确诊治率更高，且成本更低。单因素敏感性分析和概率敏感性分析均证实结果的稳健性。结论：中国早中期和晚期NSCLC患者在进行免疫单药治疗时，SP263检测方案是具有成本效果的PD-L1检测方案。

关键词: PD-L1检测, 非小细胞肺癌, 免疫单药治疗, 成本效果分析

Abstract:

Background and purpose: According to the latest data from the National Cancer Center, the incidence rate and mortality of lung cancer in China rank first among all malignant tumors, and 85% are non-small cell lung cancer (NSCLC). In recent years, immunotherapy based on programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) has made breakthrough progress in lung cancer, bringing more survival benefits to lung cancer patients. This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC, and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China. Methods: From a healthcare system perspective, a decision-tree model was constructed to simulate the cost and effectiveness (percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines) of employing Ventana PD-L1 IHC (SP263) assay, PD-L1 IHC 22C3 pharmDx, and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China, respectively. The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis. The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis. Results: When considering atezolizumab monotherapy following chemotherapy for early to mid-stage (Ⅱ A-Ⅲ B) NSCLC patients, in comparison to the 22C3 assay or 22C3 antibody concentrate, the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient. The SP263 assay, which can guide multiple ICIs monotherapies (e.g., atezolizumab, pembrolizumab) for advanced (Ⅳ) NSCLC patients, was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate. One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results. Conclusion: The Ventana PD-L1 IHC SP263 assay was cost-effective, compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

Key words: PD-L1 testing, NSCLC, Immunotherapy, Cost-effectiveness analysis

李媛, 郭凌川, 袁勇, 郑强, 金燕, 明坚. PD-L1检测指导中国非小细胞肺癌患者免疫治疗的成本效果分析[J]. 中国癌症杂志, 2025, 35(2): 237-248.

LI Yuan, GUO Lingchuan, YUAN Yong, ZHENG Qiang, JIN Yan, MING Jian. Cost-effectiveness of PD-L1 testing to guide immunotherapy for patients with non-small cell lung cancer in China[J]. China Oncology, 2025, 35(2): 237-248.

图/表 12

图1

表1

模型参数汇总"

Parameters	Values	Data sources
Diagnostic performance
SP263 acceptable rate	90.55%	NordiQC, PD-L1 (lung) assessment run C1-C5 (2017-2019)^[8]*
22C3 assay acceptable rate	85.81%
22C3 antibody concentrate acceptable rate	75.63%
SP263 false positive, false negative	1.32%, 8.13%
22C3 assay false positive, false negative	1.98%, 12.21%
22C3 antibody concentrate false positive, false negative	3.40%, 20.97%
Proportion of patients with positive PD-L1 expression
Proportion of early to mid-stage NSCLC patients with positive PD-L1 expression (TPS/TC≥1%)	33.29%	Zheng Q, et al. 2021^[9]
Proportion of advanced NSCLC patients with positive PD-L1 expression (TPS/TC≥50%)	23.76%
Proportion of drug treatment
Proportion of early to mid-stage NSCLC patients receiving BSC after positive PD-L1 testing	60.00%	Expert interviews
Proportion of advanced NSCLC patients receiving chemotherapy after positive PD-L1 testing	19.00%
Proportion of advanced NSCLC patients treated with atezolizumab and pembrolizumab after positive PD-L1 testing (TPS/TC≥50%)	32.00%, 68.00%
Clinical parameters
mDFS in early to mid-stage NSCLC patients treated with atezolizumab monotherapy	Not estimable	IMPOWER 010 ^[10]
mDFS in early to mid-stage NSCLC patients treated with BSC monotherapy	35.3 months	IMPOWER 010
mPFS in advanced NSCLC patients treated with atezolizumab monotherapy	8.2 months	IMPOWER 110 ^[11]
mPFS in advanced NSCLC patients treated with chemotherapy	5.0 months	IMPOWER 110
mPFS in advanced NSCLC patients treated with pembrolizumab monotherapy	10.3 months	KEYNOTE 024 ^[12]
mPFS in advanced NSCLC patients treated with chemotherapy	6.0 months	KEYNOTE 024
Cost parameters (¥)
Testing cost
PD-L1 testing cost	¥1 450	Median price charges for medical services by province in China
Drug treatment cost
Atezolizumab price (1 200 mg)	¥ 32 800	China Tendering Drugs Database
Pembrolizumab price (100 mg)	¥17 918	China Tendering Drugs Database
BSC cost (3 weeks)	¥1 887	Chen P, et al. 2022 [13]
Cisplatin (10 mg)	¥10	China Tendering Drugs Database
Carboplatin (50 mg)	¥67	China Tendering Drugs Database
Pemetrexed (100 mg)	¥311	China Tendering Drugs Database
Irinotecan (10 mg)	¥222	China Tendering Drugs Database
Gemcitabine (200 mg)	¥43	China Tendering Drugs Database
Docetaxel (20 mg)	¥147	China Tendering Drugs Database
Adverse events administration costs
Anemia	¥6 434	Gu X, et al. 2019^[14]
Fatigue	¥746	Wu B, et al. 2012^[15]
Pneumonia	¥2 500	Expert interviews
Thrombocytopenia	¥9 693	Tang Y Q, 2023^[16]
Neutropenia	¥3 510	Shi F H, 2021^[17]
Healthcare resource utilization costs
Complete blood count	¥10	Median price charges for medical services by province in China
Comprehensive metabolic panel	¥188
Chest CT	¥173
MRI scan	¥419
PET/CT	¥6 600
Ultrasound scan	¥30
Whole body bone scan	¥450
Tumor markers	¥229

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Testing methods	Cost	Diagnose and treatment rate/%	Incremental cost (Δcost)	Incremental diagnose and treatment rate (Δrate)/%	ICER (Δcost/Δrate)
SP263 assay	¥70 841	72.47
22C3 assay	¥70 483	68.67	¥359	3.80	9 449
22C3 antibody concentrate	¥69 713	60.52	¥1 129	11.94	9 449

Testing methods	Cost	Diagnose and treatment rate/%	Incremental cost (Δcost)	Incremental diagnose and treatment rate (Δrate)/%	ICER (Δcost/Δrate)
SP263 assay	¥58 306	86.46
22C3 assay	¥61 720	81.93	-¥3 414	4.53	SP263 was superior
22C3 antibody concentrate	¥61 365	72.21	-¥3 059	14.25	SP263 was superior