F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Roche Products Ltd, Welwyn, United Kingdom.
JCO Clin Cancer Inform. 2021 Apr;5:450-458. doi: 10.1200/CCI.20.00149.
External control (EC) arms derived from electronic health records (EHRs) can provide appropriate comparison groups when randomized control arms are not feasible, but have not been explored for metastatic colorectal cancer (mCRC) trials. We constructed EC arms from two patient-level EHR-derived databases and evaluated them against the control arm from a phase III, randomized controlled mCRC trial.
IMblaze370 evaluated atezolizumab with or without cobimetinib versus regorafenib in patients with mCRC. EC arms were constructed from the Flatiron Health (FH) EHR-derived de-identified database and the combined FH/Foundation Medicine Clinico-Genomic Database (CGDB). IMblaze370 eligibility criteria were applied to the EC cohorts. Propensity scores and standardized mortality ratio weighting were used to balance baseline characteristics between the IMblaze370 and EC arms; balance was assessed using standardized mean differences. Kaplan-Meier method estimated median overall survival (OS). Cox proportional hazards models estimated hazard ratios with bootstrapped 95% CIs to compare differences in OS between study arms.
The FH EC included 184 patients; the CGDB EC included 108 patients. Most characteristics were well-balanced (standardized mean difference < 0.1) between each EC arm and the IMblaze370 population. Median OS was similar between the IMblaze370 control arm (8.5 months [95% CI, 6.41 to 10.71]) and both EC arms: FH (8.5 months [6.93 to 9.92]) and CGDB (8.8 months [7.85 to 9.92]). OS comparisons between the IMblaze370 experimental arm and the FH EC (hazard ratio, 0.85 [0.64 to 1.14]) and CGDB EC (0.86 [0.65 to 1.18]) yielded similar results as the comparison with the IMblaze370 control arm (1.01 [0.75 to 1.37]).
EC arms constructed from the FH database and the CGDB closely replicated the control arm from IMblaze370. EHR-derived EC arms can provide meaningful comparators in mCRC trials when recruiting a randomized control arm is not feasible.
当随机对照臂不可行时，源自电子健康记录 (EHR) 的外部对照 (EC) 臂可以提供合适的对照组，但尚未在转移性结直肠癌 (mCRC) 试验中进行探索。我们从两个基于患者水平的 EHR 衍生数据库构建了 EC 臂，并将其与 III 期随机对照 mCRC 试验的对照臂进行了比较。
IMblaze370 评估了 atezolizumab 联合或不联合 cobimetinib 与regorafenib 治疗 mCRC 患者的疗效。EC 臂是从 Flatiron Health（FH）EHR 衍生的去识别数据库和 FH/Foundation Medicine Clinico-Genomic Database（CGDB）组合数据库构建的。将 IMblaze370 的纳入标准应用于 EC 队列。使用倾向评分和标准化死亡率比加权来平衡 IMblaze370 和 EC 臂之间的基线特征；使用标准化均数差异来评估平衡。Kaplan-Meier 法估计中位总生存期（OS）。Cox 比例风险模型估计风险比，并使用 bootstrap 95%CI 来比较研究臂之间 OS 的差异。
FH EC 包括 184 名患者；CGDB EC 包括 108 名患者。每个 EC 臂与 IMblaze370 人群之间的大多数特征都很好地平衡（标准化均数差异<0.1）。IMblaze370 对照臂（8.5 个月[95%CI，6.41 至 10.71]）和两个 EC 臂（FH 8.5 个月[6.93 至 9.92]和 CGDB 8.8 个月[7.85 至 9.92]）之间的中位 OS 相似。与 IMblaze370 实验臂相比，FH EC（风险比，0.85[0.64 至 1.14]）和 CGDB EC（风险比，0.86[0.65 至 1.18]）的 OS 比较结果与与 IMblaze370 对照臂的比较结果相似（1.01[0.75 至 1.37]）。
源自 FH 数据库和 CGDB 的 EC 臂紧密复制了来自 IMblaze370 的对照臂。当招募随机对照臂不可行时，EHR 衍生的 EC 臂可为 mCRC 试验提供有意义的对照。
