Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Levine Cancer Institute, Charlotte, NC, USA.
J Natl Cancer Inst. 2022 Jan 11;114(1):60-67. doi: 10.1093/jnci/djab187.
Disease-free survival (DFS) with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival (OS) with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence in patients who received adjuvant FOLFOX. Hence, reevaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed.
Individual patient data from 9 randomized studies conducted between 1998 and 2009 were included; 3 trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (RWLS2) and Copula bivariate (RCopula2) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation.
Data from a total of 18 396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (T1-3 and N1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high or deficient mismatch repair tumors. Trial-level correlation between 3-year DFS and 5-year OS remained strong (RWLS2 = 0.82, 95% CI = 0.67 to 0.98; RCopula2 = 0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results.
Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.
在辅助化疗结肠癌（CC）试验中，中位随访 3 年的无病生存（DFS）经验证可替代中位随访 5 年的总生存（OS）。最近的数据显示，接受辅助 FOLFOX 治疗的患者在复发后 OS 和生存进一步改善。因此，需要重新评估 DFS 与 OS 之间的关联，并确定 OS 的最佳随访时间，以帮助其在未来辅助试验中应用。
纳入 1998 年至 2009 年期间进行的 9 项随机研究的个体患者数据；3 项试验检测了生物制剂。使用线性回归（RWLS2）和 Copula 二元（RCopula2）模型评估了中位随访时间为 3 年的 DFS 与 5 至 6.5 年 OS 的治疗效果估计值之间的试验级替代关系，并报告了 95%置信区间（CI）。对于 R2，接近 1 的值表示相关性越强。
共分析了 18396 例患者的数据（中位年龄=59 岁；54.0%为男性），其中 54.1%的患者肿瘤为低危（T1-3 和 N1），31.6%的患者 KRAS 突变，12.3%的患者 BRAF 突变，12.4%的患者微卫星不稳定或错配修复缺陷高。中位 OS 随访时间延长后，3 年 DFS 与 5 年 OS 之间的试验级相关性仍然较强（RWLS2=0.82，95%CI=0.67 至 0.98；RCopula2=0.92，95%CI=0.83 至 1.00）。仅对检测生物制剂的试验进行的分析得出了一致的结果。
3 年 DFS 仍然是辅助 CC 试验中 5 年 OS 的有效替代终点。OS 随访 6 年后，相关性可能会增强。
