评估 6501 例接受氟尿嘧啶、亚叶酸钙和奥沙利铂治疗的 III 期结肠癌患者 10 年期间结局变化：ACCENT 数据库的汇总分析。

Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database.

机构信息

Levine Cancer Institute, Carolinas HealthCare System, Charlotte, USA.

Department of Health Science Research, Mayo Clinic, Rochester, USA.

出版信息

Ann Oncol. 2020 Apr;31(4):480-486. doi: 10.1016/j.annonc.2019.12.007. Epub 2020 Jan 16.

DOI:10.1016/j.annonc.2019.12.007

PMID:32085892

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10688027/

Abstract

BACKGROUND

Since 2004, adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for patients with resected colon cancer. Herein we examine the change of outcomes over a 10-year period in patients with stage III colon cancer who received this regimen.

PATIENTS AND METHODS

Individual patient data from the ACCENT database was used to compare the outcomes in older (1998-2003) and newer (2004-2009) treatment eras for patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. The outcomes were compared between the two groups by the multivariate Cox proportional-hazards model adjusting for age, sex, performance score, T stage, N stage, tumor sidedness, and histological grade.

RESULTS

A total of 6501 patients with stage III colon cancer who received adjuvant FOLFOX or FLOX in six randomized trials were included in the analysis. Patients enrolled in the new era group experienced statistically significant improvement in time to recurrence [3-year rate, 76.1% versus 73.0%; adjusted hazard ratio (HR) = 0.83 (95% CI, 0.74-0.92), P = 0.0008], disease-free survival (DFS) [3-year rate, 74.7% versus 72.3%; HR = 0.88 (0.79-0.98), P = 0.024], survival after recurrence (SAR) [median time, 27.0 versus 17.7 months; HR = 0.65 (0.57-0.74), P < 0.0001], and overall survival (OS) [5-year rate, 80.9% versus 75.7%; HR = 0.78 (0.69-0.88), P < 0.0001]. The improved outcomes remained in patients diagnosed at 45 years of age or older, low-risk patients (T1-3 and N1), left colon, mismatch repair proficient (pMMR), BRAF, and KRAS wild-type tumors.

CONCLUSION

Improved outcomes were observed in patients with stage III colon cancer enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared with patients in the older era. Prolonged SAR calls for revalidation of 3-year DFS as the surrogate endpoint of OS in adjuvant clinical trials and reevaluation of optimal follow-up of OS to confirm the trial findings based on the DFS endpoints.

CLINICAL TRIALS NUMBERS

NCT00079274; NCT00096278; NCT00004931; NCT00275210; NCT00265811; NCT00112918.

摘要

背景

自 2004 年以来，辅助 5-氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX 或 FLOX）一直是结肠癌患者的标准治疗方法。在此，我们研究了在接受这种方案治疗的 III 期结肠癌患者中，10 年来结局的变化。

患者和方法

使用 ACCENT 数据库的个体患者数据，比较了接受辅助 FOLFOX 或 FLOX 治疗的 III 期结肠癌患者在较老（1998-2003 年）和较新（2004-2009 年）治疗时期的结局。通过多变量 Cox 比例风险模型，根据年龄、性别、表现评分、T 分期、N 分期、肿瘤侧别和组织学分级，对两组之间的结局进行了比较。

结果

共有 6501 例接受六项随机试验中辅助 FOLFOX 或 FLOX 治疗的 III 期结肠癌患者纳入分析。在新治疗组中，患者的复发时间[3 年率，76.1%与 73.0%；调整后的危险比（HR）=0.83（95%CI，0.74-0.92），P=0.0008]、无病生存（DFS）[3 年率，74.7%与 72.3%；HR=0.88（0.79-0.98），P=0.024]、复发后生存（SAR）[中位时间，27.0 与 17.7 个月；HR=0.65（0.57-0.74），P<0.0001]和总生存（OS）[5 年率，80.9%与 75.7%；HR=0.78（0.69-0.88），P<0.0001]均有统计学显著改善。在诊断年龄在 45 岁或以上、低危患者（T1-3 和 N1）、左结肠癌、错配修复功能正常（pMMR）、BRAF 和 KRAS 野生型肿瘤的患者中，改善的结局仍然存在。