Mhatre Shivani K, Machado Robson J M, Ton Thanh G N, Trinh Huong, Mazieres Julien, Rittmeyer Achim, Bretscher Michael T
Genentech, Inc., South San Francisco, California, USA.
Roche Products Ltd., Welwyn Garden City, UK.
Clin Pharmacol Ther. 2023 Dec;114(6):1313-1322. doi: 10.1002/cpt.3045. Epub 2023 Sep 28.
Evaluating cancer treatments in real-world data (RWD) requires informative endpoints. This study replicated the atezolizumab and docetaxel arms of the OAK trial using RWD and compared progression-free survival (PFS) outcomes derived from abstracted physician's notes in RWD (rwPFS) against PFS outcomes derived from the clinical trial PFS (ctPFS). Atezolizumab and docetaxel arms of the phase III OAK randomized controlled trial (RCT; NCT02008227) were replicated in a US nationwide real-world database using selected OAK inclusion/exclusion criteria and propensity score-based adjustment for baseline prognostic variables. Concordance of outcomes was assessed using Kaplan-Meier medians and hazard ratios (HRs). The RWD cohorts comprised 133 patients on atezolizumab and 479 patients on docetaxel. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. The rwPFS and ctPFS outcomes showed better concordance for docetaxel (2.99 vs. 3.52 months; HR: 0.99, 95% confidence interval (CI): 0.85-1.15) than for atezolizumab (3.71 vs. 2.76 months; HR: 0.8, 95% CI: 0.61-1.02). Excluding events labeled "pseudo-progression" from both RWD and RCT improved concordance for atezolizumab (4.24 vs. 4.14 months; HR: 0.95, 95% CI: 0.70-1.25). These findings were robust across sensitivity analyses. Replicating RCTs using RWD and comparing outcomes can help characterize RWD endpoints. Similarity of results between rwPFS and ctPFS at the cohort level may depend on drug category, highlighting the need for further studies to verify and understand when the corresponding outcomes can be compared, including within the same patient.
在真实世界数据（RWD）中评估癌症治疗方法需要有信息量的终点指标。本研究使用RWD复制了OAK试验中阿特珠单抗和多西他赛治疗组，并将从RWD中提取的医生记录得出的无进展生存期（PFS）结果（rwPFS）与从临床试验PFS（ctPFS）得出的PFS结果进行比较。采用选定的OAK纳入/排除标准以及基于倾向评分对基线预后变量进行调整，在美国全国性真实世界数据库中复制了III期OAK随机对照试验（RCT；NCT02008227）的阿特珠单抗和多西他赛治疗组。使用Kaplan-Meier中位数和风险比（HR）评估结果的一致性。RWD队列包括133例接受阿特珠单抗治疗的患者和479例接受多西他赛治疗的患者。调整后，RCT治疗组与相应的RWD队列之间的预后变量达到平衡。与阿特珠单抗相比（3.71对2.76个月；HR：0.8，95%置信区间（CI）：0.61 - 1.02），多西他赛的rwPFS和ctPFS结果显示出更好的一致性（2.99对3.52个月；HR：0.99，95%CI：0.85 - 1.15）。从RWD和RCT中排除标记为“假性进展”的事件后，阿特珠单抗的一致性得到改善（4.24对4.14个月；HR：0.95，95%CI：0.70 - 1.25）。这些发现在敏感性分析中是稳健的。使用RWD复制RCT并比较结果有助于表征RWD终点指标。队列水平上rwPFS和ctPFS结果的相似性可能取决于药物类别，这突出表明需要进一步研究来验证和理解何时可以比较相应结果，包括在同一患者体内。
