Data_Sheet_1_Effectiveness and cost-effectiveness analysis of 11 treatment paths, seven first-line and three second-line treatments for Chinese patients with advanced wild-type squamous non-small cell lung cancer: A sequential model.DOCX

BackgroundA total of 11 treatment sequences for advanced wild-type squamous non-small cell lung cancer are recommended by Chinese Society of Clinical Oncology Guidelines, consisting of seven first-line and three second-line treatments. Five of these treatments were newly approved in China between 2021 and 2022. We evaluated the effectiveness and cost-effectiveness of these strategies from the Chinese healthcare system perspective.
MethodsNetwork meta-analysis with non-proportional hazards was used to calculate the relative efficacy between interventions. A sequential model was developed to estimate costs and quality-adjusted life years (QALY) for treatment sequences with first-line platinum- and paclitaxel-based chemotherapy (SC) with or without nedaplatin, tislelizumab, camrelizumab, sintilimab, sugemalimab or pembrolizumab, followed by second-line docetaxel, tislelizumab or nivolumab. SC and docetaxel were used as comparators for first-line and second-line treatments, respectively. QALY and incremental cost-effectiveness ratio (ICER) were used to evaluate effectiveness and cost-effectiveness, respectively. Cost-effective threshold was set as USD 19,091. Subgroup analysis was conducted to determine the best first-line and second-line therapy.
ResultsPembrolizumab + SC, followed by docetaxel (PED) was the most effective treatment sequence. QALYs for patients received SC, nedaplatin + SC, tislelizumab + SC, sintilimab + SC, camrelizumab + SC, sugemalimab + SC, pembrolizumab + SC followed by docetaxel were 0.866, 0.906, 1.179, 1.266, 1.179, 1.266, 1.603, 1.721, 1.807; QALYs for SC, nedaplatin + SC followed by tislelizumab were 1.283, 1.301; QALYs for SC, nedaplatin + SC followed by nivolumab were 1.353, 1.389. Camrelizumab + SC, followed by docetaxel (CAD) was the most cost-effective. Compared to SC with or without nedaplatin, tislelizumab, or sintilimab followed by docetaxel, ICERs of CAD were USD 12,276, 13,210, 6,974, 9,421/QALY, respectively. Compared with nedaplatin or SC followed by tislelizumab, the ICERs of CAD were USD 4,183, 2,804/QALY; CAD was dominant compared with nedaplatin or SC followed by nivolumab; The ICER of sugemalimab + SC followed by docetaxel and PED were USD 522,023, 481,639/QALY compared with CAD. Pembrolizumab + SC and camrelizumab + SC were the most effective and cost-effective first-line options, respectively; tislelizumab was the most effective and cost-effective second-line therapy. Tislelizumab used in second-line was more effective than first-line, no significant differences between their cost-effectiveness. Sensitivity and scenario analysis confirmed robustness of the results.
ConclusionsPED and CAD are the most effective and cost-effective treatment sequence, respectively; pembrolizumab + SC and camrelizumab + SC are the most effective and cost-effective first-line choice, respectively; tislelizumab is the most effective and cost-effective second-line choice.

研究背景：中国临床肿瘤学会（Chinese Society of Clinical Oncology）指南推荐了11种针对晚期野生型鳞状非小细胞肺癌的治疗序贯方案，包含7种一线治疗方案与3种二线治疗方案。其中5种治疗方案于2021至2022年间在中国首次获批。本研究从中国医疗卫生系统视角出发，评估上述策略的有效性与成本效益。

研究方法：本研究采用非比例风险模型下的网络Meta分析（network meta-analysis）计算不同干预措施间的相对疗效；构建序贯模型以估算治疗序贯方案的成本与质量调整生命年（quality-adjusted life years, QALY），所涉及的一线治疗方案为以铂类及紫杉醇为基础的化疗方案（platinum- and paclitaxel-based chemotherapy, SC）联合或不联合奈达铂（nedaplatin）、替雷利珠单抗（tislelizumab）、卡瑞利珠单抗（camrelizumab）、信迪利单抗（sintilimab）、舒格利单抗（sugemalimab）或帕博利珠单抗（pembrolizumab），后续二线治疗方案为多西他赛（docetaxel）、替雷利珠单抗或纳武利尤单抗（nivolumab）。分别以SC方案与多西他赛作为一线、二线治疗的对照干预措施；分别以QALY与增量成本效果比（incremental cost-effectiveness ratio, ICER）评估治疗有效性与成本效益。本研究设定的成本效益阈值为19091美元；通过亚组分析明确最优一线与二线治疗方案。

研究结果：帕博利珠单抗联合SC序贯多西他赛（PED）为有效性最优的治疗序贯方案。接受SC方案、奈达铂联合SC方案、替雷利珠单抗联合SC方案、信迪利单抗联合SC方案、卡瑞利珠单抗联合SC方案、舒格利单抗联合SC方案、帕博利珠单抗联合SC序贯多西他赛的患者，其QALY分别为0.866、0.906、1.179、1.266、1.179、1.266、1.603、1.721、1.807；接受SC方案、奈达铂联合SC方案序贯替雷利珠单抗的患者QALY分别为1.283、1.301；接受SC方案、奈达铂联合SC方案序贯纳武利尤单抗的患者QALY分别为1.353、1.389。卡瑞利珠单抗联合SC序贯多西他赛（CAD）为成本效益最优的治疗序贯方案。相较于SC方案、奈达铂联合SC方案、替雷利珠单抗联合SC方案、信迪利单抗联合SC方案序贯多西他赛，CAD的ICER分别为12276美元、13210美元、6974美元、9421美元每QALY；相较于奈达铂联合SC方案或SC方案序贯替雷利珠单抗，CAD的ICER分别为4183美元、2804美元每QALY；相较于奈达铂联合SC方案或SC方案序贯纳武利尤单抗，CAD具有绝对成本效益优势。相较于CAD，舒格利单抗联合SC序贯多西他赛与PED的ICER分别为522023美元、481639美元每QALY。帕博利珠单抗联合SC与卡瑞利珠单抗联合SC分别为有效性最优与成本效益最优的一线治疗方案；替雷利珠单抗为有效性与成本效益均最优的二线治疗方案。二线使用替雷利珠单抗的疗效优于一线使用，二者的成本效益无显著差异。敏感性分析与情景分析证实了本研究结果的稳健性。

研究结论：本研究结果显示，PED与CAD分别为有效性最优与成本效益最优的治疗序贯方案；帕博利珠单抗联合SC与卡瑞利珠单抗联合SC分别为有效性最优与成本效益最优的一线治疗方案；替雷利珠单抗为有效性与成本效益均最优的二线治疗方案。