Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803.
Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803.
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DOI：
10.1016/j.ejca.2010.12.015
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发表时间：
2011-05
影响因子：
8.4
通讯作者：
de Gramont, A.
中科院分区：
文献类型：
--
作者：
Sargent, D.;Shi, Q.;Yothers, G.;Van Cutsem, E.;Cassidy, J.;Saltz, L.;Wolmark, N.;Bot, B.;Grothey, A.;Buyse, M.;de Gramont, A.
ACCENT组先前建立了无病生存期（DFS），中位随访时间为2年或3年，以预测II期和III期结肠癌的5年总生存期（5年OS）。ACCENT进一步提出：（1）在III期DFS和OS之间的相关性强于II期，（2）在最近的试验中，证明DFS/OS代孕需要6或7年。口服氟尿嘧啶、奥沙利铂和伊立替康试验中终点之间的关系未知。在1997-2002年未纳入既往分析的6项III期试验中，检查了2年和3年DFS与5年和6年OS的治疗效果风险比（HR）之间的相关性。分析了12，676例患者的个体数据;两项试验分别测试了奥沙利铂、伊立替康和口服治疗与5-FU/LV。2/3年DFS和5/6年OS HR之间的总体相关性为中度至较差（简单R2测量值：0.58至0.76，基于模型的R2：0.17至0.49）。在III期患者中，相关性增加（基于模型的R2≥0.79）。观察治疗对2年DFS的影响，准确地观察5/6年OS对总体和III期患者的影响。在最近的细胞毒化疗试验中，2年或3年DFS HR高度预测III期患者的5年和6年OS HR，但II期患者则不然。在所有患者中，6年OS的DFS/OS相关性更强，因此建议至少随访6年以评估OS获益。这些数据支持DFS作为检测细胞毒性药物的III期结肠癌试验的主要终点。由NCI赠款CA-25224资助给马约诊所，以支持中北部癌症治疗小组。
The ACCENT group previously established disease-free survival (DFS) with 2 or 3 years median follow-up to predict 5 year overall survival (5yr OS) in stage II and III colon cancer. ACCENT further proposed (1) a stronger association between DFS and OS in stage III than II, and (2) 6 or 7 years necessary to demonstrate DFS/OS surrogacy in recent trials. The relationship between endpoints in trials with oral fluoropyrimidines, oxaliplatin, and irinotecan is unknown. Associations between the treatment effect hazard ratios (HRs) on 2 and 3yr DFS, and 5 and 6yr OS were examined in 6 phase III trials not included in prior analyses from 1997-2002. Individual data for 12,676 patients were analyzed; two trials each tested oxaliplatin, irinotecan, and oral treatment vs 5-FU/LV. Overall association between 2/3 yr DFS and 5/6 yr OS HRs was modest to poor (simple R2 measures: 0.58 to 0.76, model-based R2: 0.17 to 0.49). In stage III patients, the association increased (model-based R2≥0.79). Observed treatment effects on 2 yr DFS accurately 5/6 yr OS effects overall and in stage III patients. In recent trials of cytotoxic chemotherapy, 2 or 3yr DFS HRs are highly predictive of 5 and 6yr OS HRs in stage III but not stage II patients. In all patients the DFS/OS association is stronger for 6yr OS, thus at least 6 year follow-up is recommended to assess OS benefit. These data support DFS as the primary endpoint for stage III colon cancer trials testing cytotoxic agents. Funded by NCI Grant CA-25224 to the Mayo Clinic to support the North Central Cancer Treatment Group.
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