Supplementary materials: A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer

These are peer-reviewed supplementary materials for the article 'A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer' published in the Journal of Comparative Effectiveness Research.
Additional Methodology
Survival analysisProportional hazards assumptionPiecewise constant hazard ratios modelsFigures
Fig. S1: Network of evidence for first-line to progression - progression-freeFig. S2: Network of evidence for first-line to progression - overall survivalFig. S3: Network of evidence for first-line to progression - progression-free survival and overall survival for the PD-L1 ≥50% subgroup survivalTables
Table S1a: Medline search terms used for SLRTable S1b: Embase search terms used for SLRTable S1c: Cochrane CENTRAL search terms used for SLRTable S2: PICOS StatementTable S3: Reasons for exclusion of studies from the first-line to progression NMA base case analysesTable S4: Reasons for exclusion of studies from the second-line NMA base case analysesData Inputs
Table S5: Input data for first-line to progression PFS – HRTable S6: Input data for first-line to progression OS – HRTable S7: Input data for second-line PFS – HRTable S8: Input data for second-line PFS – medianTable S9: Input data for second-line OS – HRTable S10: Input data for second-line OS – medianResults
Table S11: Model assessment statistics for the piecewise constant hazard ratio survival models on both OS and PFSTable S12: Pairwise hazard ratios for first-line to progression OS (using random effects model)Table S13: Pairwise hazard ratios for first-line to progression PFS (using random effects model)Table S14: Piecewise analysis: pairwise hazard ratios for first-line to progression - OS (using random effects model)Table S15: Piecewise analysis: pairwise hazard ratios for first-line to progression PFS (using random effects model)Table S16: Pairwise hazard ratios for first-line to progression OS (using fixed effects model) in the PD-L1 ≥50 subgroupTable S17: Pairwise hazard ratios for first-line to progression OS (using random effects model) in the PD-L1 ≥50 subgroupTable S18: Pairwise hazard ratios for first-line to progression PFS (using fixed effects model) in the PD-L1 ≥50 subgroupTable S19: Pairwise hazard ratios for first-line to progression PFS (using random effects model) in the PD-L1 ≥50 subgroupTable S20: Pairwise hazard ratios (and credible intervals) for second-line overall survival (using random effects model)Table S21: Pairwise hazard ratios (and credible intervals) for second-line progression-free survival (using random effects model)References
Introduction: In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was conducted to compare the relative efficacy of these treatments. Materials & methods: A systematic literature review of randomized controlled trials evaluating first-line-to-progression and second-line treatments for advanced NsqNSCLC informed Bayesian NMAs for overall survival (OS) and progression-free survival (PFS) end points. Results: Among first-line-to-progression treatments, pembrolizumab + pemetrexed + platinum showed the greatest OS benefit versus other regimens and a PFS benefit versus all but three regimens. Among second-line treatments, an OS benefit was seen for atezolizumab, nivolumab and pembrolizumab versus docetaxel. Conclusion: Pembrolizumab + pemetrexed + platinum showed the maximum OS benefit in the first-line setting. In the second-line setting, anti-PD-1/anti-PD-L1 monotherapies were better than docetaxel.

本数据集为发表于《比较效果研究期刊》（Journal of Comparative Effectiveness Research）的论文《针对晚期非鳞状非小细胞肺癌的免疫治疗方案网络meta分析》的同行评议补充材料。

附加方法
生存分析：比例风险假设、分段恒定风险比模型

图表
图S1：一线治疗至进展的无进展生存证据网络图
图S2：一线治疗至进展的总生存证据网络图
图S3：PD-L1≥50%亚组中，一线治疗至进展的无进展生存与总生存证据网络图

表格
表S1a：系统性文献回顾（systematic literature review, SLR）所用Medline检索策略
表S1b：系统性文献回顾（SLR）所用Embase检索策略
表S1c：系统性文献回顾（SLR）所用Cochrane CENTRAL检索策略
表S2：PICOS原则声明
表S3：一线治疗至进展的网络meta分析基础案例分析中研究排除原因
表S4：二线治疗网络meta分析基础案例分析中研究排除原因

数据输入
表S5：一线治疗至进展无进展生存风险比（hazard ratio, HR）输入数据
表S6：一线治疗至进展总生存风险比（HR）输入数据
表S7：二线治疗无进展生存风险比（HR）输入数据
表S8：二线治疗无进展生存中位值输入数据
表S9：二线治疗总生存风险比（HR）输入数据
表S10：二线治疗总生存中位值输入数据

结果
表S11：针对总生存（overall survival, OS）与无进展生存（progression-free survival, PFS）的分段恒定风险比生存模型评估统计量
表S12：采用随机效应模型的一线治疗至进展总生存配对风险比
表S13：采用随机效应模型的一线治疗至进展无进展生存配对风险比
表S14：分段分析：采用随机效应模型的一线治疗至进展总生存配对风险比
表S15：分段分析：采用随机效应模型的一线治疗至进展无进展生存配对风险比
表S16：PD-L1≥50%亚组中，采用固定效应模型的一线治疗至进展总生存配对风险比
表S17：PD-L1≥50%亚组中，采用随机效应模型的一线治疗至进展总生存配对风险比
表S18：PD-L1≥50%亚组中，采用固定效应模型的一线治疗至进展无进展生存配对风险比
表S19：PD-L1≥50%亚组中，采用随机效应模型的一线治疗至进展无进展生存配对风险比
表S20：采用随机效应模型的二线治疗总生存配对风险比（及可信区间）
表S21：采用随机效应模型的二线治疗无进展生存配对风险比（及可信区间）

参考文献
引言：在缺乏针对晚期非鳞状非小细胞肺癌（nonsquamous non-small cell lung cancer, NsqNSCLC）免疫治疗方案的头对头对比试验的背景下，本研究开展了一项网络meta分析（network meta-analysis, NMA）以比较各类治疗方案的相对疗效。
材料与方法：针对晚期非鳞状非小细胞肺癌的一线至进展治疗与二线治疗方案，本研究开展了系统性文献回顾，纳入评估相关随机对照试验，以此为针对总生存（OS）与无进展生存（PFS）终点的贝叶斯网络meta分析提供依据。
结果：在一线至进展治疗方案中，帕博利珠单抗+培美曲塞+铂类方案相较于其他所有方案均展现出最显著的总生存获益，且相较于除3种方案外的其余所有方案均具有无进展生存获益。在二线治疗方案中，阿替利珠单抗、纳武利尤单抗与帕博利珠单抗相较于多西他赛均展现出总生存获益。
结论：帕博利珠单抗+培美曲塞+铂类方案在一线治疗场景中展现出最优总生存获益。在二线治疗场景中，抗PD-1/抗PD-L1单药治疗方案优于多西他赛。