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

<b>These are peer-reviewed supplementary materials for the article '</b><b>A network meta-analysis of </b><b>immunotherapy-based treatments for </b><b>advanced nonsquamous non-small cell </b><b>lung cancer</b><b>' published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Additional Methodology</b><b>Survival analysis</b><b>Proportional hazards assumption</b><b>Piecewise constant hazard ratios models</b><b>Figures</b><b>Fig. S1: </b>Network of evidence for first-line to progression - progression-free<b>Fig. S2: </b>Network of evidence for first-line to progression - overall survival<b>Fig. S3: </b>Network of evidence for first-line to progression - progression-free survival and overall survival for the PD-L1 ≥50% subgroup survival<b>Tables</b><b>Table S1a: </b>Medline search terms used for SLR<b>Table S1b: </b>Embase search terms used for SLR<b>Table S1c: </b>Cochrane CENTRAL search terms used for SLR<b>Table S2: </b>PICOS Statement<b>Table S3: </b>Reasons for exclusion of studies from the first-line to progression NMA base case analyses<b>Table S4: </b>Reasons for exclusion of studies from the second-line NMA base case analyses<b>Data Inputs</b><b>Table S5: </b>Input data for first-line to progression PFS – HR<b>Table S6:</b> Input data for first-line to progression OS – HR<b>Table S7: </b>Input data for second-line PFS – HR<b>Table S8:</b> Input data for second-line PFS – median<b>Table S9:</b> Input data for second-line OS – HR<b>Table S10:</b> Input data for second-line OS – median<b>Results</b><b>Table S11: </b>Model assessment statistics for the piecewise constant hazard ratio survival models on both OS and PFS<b>Table S12: </b>Pairwise hazard ratios for first-line to progression OS (using random effects model)<b>Table S13: </b>Pairwise hazard ratios for first-line to progression PFS (using random effects model)<b>Table S14: </b>Piecewise analysis: pairwise hazard ratios for first-line to progression - OS (using random effects model)<b>Table S15: </b>Piecewise analysis: pairwise hazard ratios for first-line to progression PFS (using random effects model)<b>Table S16: </b>Pairwise hazard ratios for first-line to progression OS (using fixed effects model) in the PD-L1 ≥50 subgroup<b>Table S17: </b>Pairwise hazard ratios for first-line to progression OS (using random effects model) in the PD-L1 ≥50 subgroup<b>Table S18: </b>Pairwise hazard ratios for first-line to progression PFS (using fixed effects model) in the PD-L1 ≥50 subgroup<b>Table S19:</b> 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)<b>References</b><b>Introduction:</b> 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. <b>Materials &amp; methods:</b> 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. <b>Results: </b>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《比较效果研究杂志》（Journal of Comparative Effectiveness Research）的文章《晚期非鳞状非小细胞肺癌免疫治疗方案的网络Meta分析》的同行评议补充材料。
附加研究方法
生存分析
比例风险假设
分段恒定风险比模型
图表
图S1：一线治疗至进展阶段的无进展生存证据网络图
图S2：一线治疗至进展阶段的总生存证据网络图
图S3：PD-L1≥50%亚组中，一线治疗至进展阶段的无进展生存与总生存证据网络图
表格
表S1a：用于系统文献回顾（Systematic Literature Review, SLR）的Medline检索式
表S1b：用于系统文献回顾的Embase检索式
表S1c：用于系统文献回顾的Cochrane CENTRAL检索式
表S2：PICOS声明
表S3：一线治疗至进展阶段网络Meta分析基础案例分析的研究排除原因
表S4：二线治疗网络Meta分析基础案例分析的研究排除原因
数据输入项
表S5：一线治疗至进展阶段无进展生存风险比输入数据
表S6：一线治疗至进展阶段总生存风险比输入数据
表S7：二线治疗无进展生存风险比输入数据
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输入数据
表S10：二线治疗总生存中位值输入数据
研究结果
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阶段总生存配对风险比
表S13：采用随机效应模型的一线治疗至进展阶段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阶段总生存配对风险比
表S15：分段分析：采用随机效应模型的一线治疗至进展阶段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阶段总生存配对风险比
表S17：PD-L1≥50%亚组中，采用随机效应模型的一线治疗至进展阶段总生存配对风险比
表S18：PD-L1≥50%亚组中，采用固定效应模型的一线治疗至进展阶段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阶段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（含可信区间）
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（含可信区间）
参考文献
引言：由于尚无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照试验，本研究开展网络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：本研究对评估晚期非鳞状非小细胞肺癌一线至进展阶段及二线治疗方案的随机对照试验开展系统文献回顾，以此为贝叶斯网络Meta分析提供数据支撑，分析结局指标包括总生存与无进展生存。
研究结果：在一线治疗至进展阶段的方案中，帕博利珠单抗+培美曲塞+铂类对比其他所有方案均展现出最显著的总生存获益，且除3种方案外，对比其余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、纳武利尤单抗及帕博利珠单抗对比多西他赛均展现出总生存获益。
结论：一线治疗场景下，帕博利珠单抗+培美曲塞+铂类可带来最优的总生存获益；二线治疗场景下，抗PD-1/抗PD-L1单药治疗疗效优于多西他赛。