RAS 野生型转移性结直肠癌患者接受 FOLFOX 加抗 EGFR 诱导治疗后的最佳维持治疗策略：随机临床试验的个体患者数据汇总分析。
Optimal maintenance strategy following FOLFOX plus anti-EGFR induction therapy in patients with RAS wild type metastatic colorectal cancer: An individual patient data pooled analysis of randomised clinical trials.
机构信息
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
出版信息
Eur J Cancer. 2023 Sep;190:112945. doi: 10.1016/j.ejca.2023.112945. Epub 2023 Jun 19.
BACKGROUND
Anti-EGFR antibodies plus doublet chemotherapy is the standard of care in RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No phase-3 level of evidence is available to guide treatment de-escalation after anti-EGFR-based first-line. Several randomised clinical trials investigated de-intensification strategies with 5-fluorouracil/leucovorin (5-FU/LV) and/or anti-EGFR.
METHODS
We performed an individual patient data pooled analysis of Valentino, Panama, MACRO-2, COIN-B trials including RAS wild-type mCRC patients who received first-line therapy with FOLFOX plus panitumumab or cetuximab followed by pre-specified maintenance strategy. Only patients who started maintenance according to the assigned arm were included. Patients were categorised by type of maintenance (i.e. 5-FU/LV, anti-EGFR or 5-FU/LV + anti-EGFR). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of maintenance; toxicity was evaluated for the maintenance treatment period.
RESULTS
A total of 518 patients were included in the pooled analysis. Overall, 123, 185 and 210 patients received maintenance with 5-FU/LV, anti-EGFR, 5-FU/LV + anti-EGFR, respectively. Median PFS was 5.6, 6.0 and 9.0 (P = 0.009) and OS was 25.7, 24.0 and 28.0 months (P = 0.134) in 5-FU/LV, anti-EGFR and 5-FU/LV + anti-EGFR arms, respectively. Monotherapy maintenance (either 5-FU/LV or anti-EGFR) was inferior to combination in terms of PFS (hazard ratios [HR] 1.26, P = 0.016) and non-significantly trending also in OS (HR 1.20, P = 0.111). An increase of overall any grade and grade ≥ 3 AEs and selected AEs was reported in combination compared to either 5-FU/LV or anti-EGFR arms.
CONCLUSIONS
This pooled analysis including four randomised phase II supports the use of 5-FU/LV plus anti-EGFR as the preferred maintenance regimen. Data provide rational for a more individualised maintenance treatment approach based on tumour and patients features.
背景
抗 EGFR 抗体联合双药化疗是 RAS/BRAF 野生型转移性结直肠癌（mCRC）的标准治疗方法。目前尚无 III 期临床试验证据可指导抗 EGFR 一线治疗后的治疗降级。几项随机临床试验研究了氟尿嘧啶/亚叶酸（5-FU/LV）和/或抗 EGFR 药物的减量化策略。
方法
我们对 Valentino、Panama、MACRO-2 和 COIN-B 试验进行了个体患者数据汇总分析，纳入了接受 FOLFOX 联合帕尼单抗或西妥昔单抗一线治疗后接受预定维持治疗策略的 RAS 野生型 mCRC 患者。仅纳入根据分配臂开始维持治疗的患者。根据维持治疗类型（即 5-FU/LV、抗 EGFR 或 5-FU/LV+抗 EGFR）对患者进行分类。从维持治疗开始计算无进展生存期（PFS）和总生存期（OS）；评估维持治疗期间的毒性。
结果
共有 518 名患者纳入汇总分析。总体而言，123、185 和 210 名患者分别接受了 5-FU/LV、抗 EGFR 和 5-FU/LV+抗 EGFR 维持治疗。5-FU/LV、抗 EGFR 和 5-FU/LV+抗 EGFR 组的中位 PFS 分别为 5.6、6.0 和 9.0 个月（P=0.009），OS 分别为 25.7、24.0 和 28.0 个月（P=0.134）。单药维持（5-FU/LV 或抗 EGFR）在 PFS 方面劣于联合治疗（风险比 [HR] 1.26，P=0.016），OS 也有非显著趋势（HR 1.20，P=0.111）。与 5-FU/LV 或抗 EGFR 组相比，联合治疗组的总体任何级别和≥3 级不良事件（AE）以及选定 AE 的发生率均有所增加。
结论
这项包括四项随机 II 期试验的汇总分析支持使用 5-FU/LV 加抗 EGFR 作为首选维持治疗方案。数据为基于肿瘤和患者特征的个体化维持治疗方法提供了依据。
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