Supplementary materials: Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC

These are supplementary materials for the article 'Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC' published in the Journal of Comparative Effectiveness Research.Supplementary Materialso Censoringo Statistical methodso Sensitivity analyseso Unadjusted resultso Propensity scoreSupplementary Table 1. Censoring rules for TTD, PFS, and OS.Supplementary Table 2. Propensity score matching.Supplementary Table 3. Comparison of results of the Cox pro-portional hazard model using BICR or investigator-assessed progression in the trial.Supplementary Table 4. Landmark analyses at 1 and 3 months for TTD and PFS.Supplementary Table 5. Sensitivity analysis of the TTD.Supplementary Table 6. Subgroup analysis by CNS status: unad-justed TTD and PFS.Supplementary Table 7. Multivariate Cox model of treatment effect by CNS status.Supplementary Figure 1. Swimmer plot of patients receiving treatment beyond progression (TBP) in the crizotinib cohort (37 out of 65 patients received TBP).Summary: Aim: Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Methods: Entrectinib-treated adults with advanced ROS1 fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65). Primary end point, time-to-treatment discontinuation (TTD); secondary end points, PFS and OS. Results: Median (95% CI) weighted TTD: 12.9 (9.9–17.4) months for entrectinib; 8.2 (6.2–9.9) months for crizotinib (weighted hazard ratio: 0.72 [0.51–1.02]). Median OS with entrectinib was not reached, weighted median OS with crizotinib was 18.5 (15.1–47.2) months. Conclusion: Entrectinib administered in clinical trials may be associated with longer TTD than a real-world crizotinib population.

本数据集为发表于《比较疗效研究杂志》之《恩曲替尼临床试验与克唑替尼真实世界数据在ROS1+非小细胞肺癌中的比较疗效分析》一文的补充材料。包括以下内容：保密规则、统计方法、敏感性分析、未调整结果、倾向得分；补充表1：TTD、PFS和OS的保密规则；补充表2：倾向得分匹配；补充表3：使用BICR或研究者评估的进展情况进行的Cox比例风险模型结果的比较；补充表4：TTD和PFS的1个月和3个月里程碑分析；补充表5：TTD的敏感性分析；补充表6：按中枢神经系统状态进行的亚组分析：未调整的TTD和PFS；补充表7：按中枢神经系统状态的多变量Cox模型治疗效果；补充图1：克唑替尼队列中接受治疗后进展（TBP）患者的游泳图（65名患者中的37名接受了TBP治疗）。摘要：目的：对于罕见疾病，在前瞻性随机试验中生成直接比较证据较为困难。真实世界队列可补充对照组。方法：来自I/II期试验（ALKA-372-001 [EudraCT2012-00148-88]、STARTRK-1 [NCT02097810]和STARTRK-2 [NCT02568267]）的94名接受恩曲替尼治疗的晚期ROS1融合阳性非小细胞肺癌成人患者与65名真实世界克唑替尼治疗队列进行比较。主要终点，治疗中断时间（TTD）；次要终点，PFS和OS。结果：恩曲替尼的中位（95% CI）加权TTD为12.9（9.9–17.4）个月；克唑替尼为8.2（6.2–9.9）个月（加权风险比：0.72 [0.51–1.02]）。恩曲替尼的中位OS未达到，克唑替尼的加权中位OS为18.5（15.1–47.2）个月。结论：临床试验中使用的恩曲替尼可能与真实世界克唑替尼人群的更长TTD相关。