There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57–0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63–2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89–3.8), while T + B (OR = 1.8, 95%CI: 0.70–4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results.

转移性结直肠癌 (mCRC) 有多种治疗方法。其中，在三联药物治疗时代，不同方案对左侧 RAS 野生型 (WT) mCRC 的临床益处仍存在不确定性。尚未进行任何研究来回答这一关键的临床问题。我们对已发布的数据和真实世界的数据进行了全面分析。首先，我们对已发表的试验进行了分析，以显示治疗左侧 RAS WT mCRC 的疗效和安全性。然后，我们启动了一项多中心真实世界研究作为验证数据集。这项研究包括六项已发表的随机对照试验 (RCT) 和总共 1925 名患者。双药方案加西妥昔单抗/帕尼单抗 (D + C/P) 在左侧 mCRC 患者中实现了最长的总生存期 (OS) (HR = 0.74, 95%CI: 0.57–0.98），而贝伐单抗的三药方案（T + B，HR = 1.1，95％CI：0.63-2.0），与贝伐单抗的双药方案（D + B）相比。D + C/P 在左侧 mCRC 患者中的总体缓解率 (ORR) 最高 (OR = 1.8, 95%CI: 0.89–3.8)，而 T + B (OR = 1.8, 95%CI: 0.70) –4.8)，与 D + B 相比。多中心真实世界队列显示左侧 mCRC 患者的双药方案加西妥昔单抗比贝伐单抗的三药方案具有更长的无进展生存期 (PFS)。安全性分析显示，三药联合贝伐单抗的不良事件（≥3级）发生率高于双药联合西妥昔单抗/帕尼单抗的不良事件发生率。这项工作展示了三种方案对左侧 RAS WT mCRC 患者的疗效和安全性的排名。双药方案加西妥昔单抗/帕尼单抗似乎比基于双药和三药的贝伐单抗方案更有效、更安全。关于该主题的进一步试验和队列分析将增加对这些结果的信心。