新辅助 FOLFOX 化疗是否能改善高危 II 期和 III 期结肠癌的预后？PRODIGE 22 期随机多中心试验的 3 年随访结果。

Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high-risk Stage II and III colon cancers? Three years' follow-up results of the PRODIGE 22 phase II randomized multicentre trial.

机构信息

Department of Digestive and Oncological Surgery, AP-HP; Hôpital Européen Georges Pompidou, Paris University, Paris, France.

Department of Hepato-gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris University, Paris, France.

出版信息

Colorectal Dis. 2021 Jun;23(6):1357-1369. doi: 10.1111/codi.15585. Epub 2021 Mar 10.

DOI:10.1111/codi.15585

PMID:33580623

Abstract

AIM

Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial.

METHOD

PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR).

RESULTS

Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed.

CONCLUSION

Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.

摘要

目的

新辅助化疗已被证明对局部晚期可切除结肠癌（CC）有价值，但对肿瘤学结局的影响尚不确定。本研究旨在报告 3 年肿瘤学结果，这是 PRODIGE 22 试验的次要终点。

方法

PRODIGE 22 是一项在 CT 扫描中高风险 T3、T4 和/或 N2 CC 患者中进行的随机多中心 II 期试验。患者在 6 个月的辅助 FOLFOX（ upfront surgery）和围手术期 FOLFOX（术前 4 个周期，术后 8 个周期；FOLFOX 围手术期）之间进行随机分组。在野生型 RAS 患者中，还增加了第三组试验围手术期 FOLFOX-西妥昔单抗。主要终点是肿瘤消退分级。次要终点是 3 年总生存率（OS）、无病生存率（DFS）、无复发生存率（RFS）和复发时间（TTR）。

结果

共有 120 例患者入组。在中期分析时，FOLFOX-西妥昔单抗组因无效而停止。其余 104 例患者为意向治疗人群。在围手术期组中，96%的患者接受了计划的 4 个新辅助周期，除 1 例外，所有患者均接受了 8 个周期的辅助 FOLFOX。在对照组中，38 例（73%）患者接受了辅助 FOLFOX。中位随访时间为 54.3 个月。两组 3 年 OS 率分别为 90.4%[风险比（HR）=0.85]，3 年 DFS、RFS 和 TTR 率分别为 76.8%和 69.2%（HR=0.94）、73%和 69.2%（HR=0.86）和 82%和 72%（HR=0.67）。围手术期和对照组。森林图未显示任何亚组的生存结果有显著差异。添加西妥昔单抗没有获益。