Oncology Outcomes Initiative, University of Calgary, Calgary, Alberta, Canada.
Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
JAMA Netw Open. 2021 Mar 1;4(3):e213587. doi: 10.1001/jamanetworkopen.2021.3587.
Several real-world oncology studies have produced findings that contradict those from randomized clinical trials. Such disparities may be associated with methodological shortcomings.
To examine the association between a shortened duration of adjuvant chemotherapy among individuals with stage III colon cancer using real-world data.
DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study included individuals diagnosed with stage III colon cancer between January 2004 and December 2015 who initiated adjuvant chemotherapy at oncology clinics within the province of Alberta, Canada. Patients were identified through record linkage of various administrative databases and were followed up until September 2017. Eligibility criteria were modeled after those used in the International Duration Evaluation of Adjuvant (IDEA) trial. A target trial emulation and naive observational analysis were conducted. Results from both cohorts were benchmarked against findings from the IDEA trial. Data analysis was conducted from March to December 2020.
A shortened duration of adjuvant 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) chemotherapy, defined as 3 to 5 months of treatment vs 6 months.
Overall survival assessed via vital statistics. The per-protocol hazard ratio (HR) was estimated using a weighted pooled logistic regression model. Subgroup analyses were conducted by treatment regimen (ie, FOLFOX vs CAPOX) and cancer stage (ie, T1-3 and N1 vs T4 or N2).
From an initial cohort of 3086 patients, 485 (16%) were eligible for inclusion in the target trial analysis. The median age was 59 years (range, 19-81 years), and 230 (47%) were women. The maximum follow-up was 11.6 years. Median overall survival was not reached. A total of 90 patients (19%) died. The 5-year Kaplan Meier overall survival estimate was 0.79 (95% CI, 0.75-0.84). Estimates from the trial emulation were similar to those from the IDEA trial. For example, a shortened duration of adjuvant chemotherapy was not associated with overall survival among patients prescribed CAPOX in the IDEA trial (HR, 0.96; 95% CI, 0.85-1.08) or in the trial emulation (HR, 0.96; 95% CI, 0.43-2.14). In contrast, the naive observational analysis suggested that a shortened duration of CAPOX was significantly associated with worse survival (HR, 3.33; 95% CI, 1.04-10.65).
In this study, the explicit emulation of a target trial better approximated results from an analogous well-conducted randomized clinical trial.
几项真实世界的肿瘤学研究得出的结果与随机临床试验的结果相矛盾。这种差异可能与方法学上的缺陷有关。
使用真实世界的数据，研究个体接受 III 期结肠癌辅助化疗时间缩短与生存时间之间的关联。
设计、地点和参与者：这项比较有效性研究纳入了 2004 年 1 月至 2015 年 12 月期间在加拿大阿尔伯塔省的肿瘤诊所接受 III 期结肠癌治疗的患者，这些患者接受了辅助化疗。通过各种行政数据库的记录链接识别患者，并随访至 2017 年 9 月。入选标准是根据国际辅助期持续时间评估（IDEA）试验中的标准制定的。进行了目标试验模拟和单纯观察性分析。两个队列的结果与 IDEA 试验的结果进行了对比。数据分析于 2020 年 3 月至 12 月进行。
辅助氟尿嘧啶/亚叶酸联合奥沙利铂（FOLFOX）或卡培他滨联合奥沙利铂（CAPOX）化疗的持续时间缩短，定义为治疗 3 至 5 个月与 6 个月。
通过生命统计评估总体生存率。使用加权的多变量逻辑回归模型估计按方案的风险比（HR）。按治疗方案（即 FOLFOX 与 CAPOX）和癌症分期（即 T1-3 和 N1 与 T4 或 N2）进行亚组分析。
从最初的 3086 名患者中，有 485 名（16%）符合目标试验分析的入选标准。中位年龄为 59 岁（范围为 19-81 岁），230 名（47%）为女性。最长随访时间为 11.6 年。中位总生存期未达到。共有 90 名患者（19%）死亡。5 年的 Kaplan-Meier 总生存率估计为 0.79（95%CI，0.75-0.84）。试验模拟的结果与 IDEA 试验相似。例如，在 IDEA 试验中（HR，0.96；95%CI，0.85-1.08）或在试验模拟中（HR，0.96；95%CI，0.43-2.14），接受 CAPOX 治疗的患者，辅助化疗持续时间缩短与总生存率无关。相比之下，单纯观察性分析表明，CAPOX 治疗时间缩短与生存时间显著相关（HR，3.33；95%CI，1.04-10.65）。
在这项研究中，明确的目标试验模拟更接近类似的精心设计的随机临床试验的结果。
