FOLFOX plus anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is an effective first-line treatment for patients with RAS-wild left-sided metastatic colorectal cancer
FOLFOX plus anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is an effective first-line treatment for patients with RAS-wild left-sided metastatic colorectal cancer
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FOLFOX 联合抗表皮生长因子受体 (EGFR) 单克隆抗体 (mAb) 是 RAS 野生型左侧转移性结直肠癌患者的有效一线治疗方法
作者：
Datian Chen;Li Li;Xiang Zhang;Guangyi Gao;Lili Shen;Jing Hu;Mi Yang;Baorui Liu;X. Qian
背景资料：以奥沙利铂为基础的化疗联合抗表皮生长因子受体（EGFR）单克隆抗体（mAb）治疗转移性结直肠癌（mCRC）的疗效仍存在争议。本荟萃分析旨在评估在RAS野生型mCRC患者中，将帕尼单抗或西妥昔单抗添加至基于奥沙利铂的化疗作为一线治疗的效果。本荟萃分析还考虑了原发肿瘤位置。研究方法：通过检索MEDLINE、EMBASE、科克伦图书馆至2017年10月，并辅以手动检索ASCO、ESMO会议摘要，确定RCT研究。通过Review Manager 5.3计算无进展生存期（PFS）和总生存期（OS）的汇总风险比（HR）以及总缓解率（ORR）的汇总比值比（OR）。结果如下：结果表明，与单独化疗相比，在RAS野生型mCRC患者的FOLFOX方案中添加抗EGFR mAb作为一线治疗可显著改善PFS（HR = 0.70; 95%置信区间[CI]：0.59-0.82; P < .0001）、OS（HR = 0.79; 95%CI：0.67-0.92; P = .003）和ORR（OR = 2.56; 95%CI：1.77-3.70; P < .00001）。然而，在RAS/BRAF野生型患者中，与单独化疗相比，抗EGFR mAb加用FLOX或XTREX方案的OS和PFS无显著差异，而FOLFOX+抗EGFR mAb显示出显著的上级OS和PFS（OS，HR = 0.77; 95% CI：0.61-0.98; P = 0.03; PFS，HR = 0.68; 95% CI：0.57-0.82; P <0.00001）。 一项包括TAILOR和PRIME研究的荟萃分析表明，当RAS野生型mCRC患者在FOLFOX方案中添加EGFR抗体时，原发肿瘤位置（PTL）可预测生存期获益（OS，左侧HR：0.71; 95% CI：0.59-0.85; P = 0.0002，右侧HR：0.90; 95% CI：0.65-1.25; P = 0.53）。 然而，PFS和ORR的HR仍然表明在右侧mCRC患者中添加抗EGFR mAb可获益。结论：抗EGFR单抗联合奥沙利铂是FOLFOX方案的良好联合用药方案。在FOLFOX中添加EGFR抗体显著改善了RAS野生型左侧mCRC患者的疗效。在RAS/BRAF野生型患者中，疗效相似。对于右侧肿瘤患者，仍然可以观察到抗EGFR mAb的获益趋势。肿瘤定位背后的分子特征迫切需要更多的探索。
Background: The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis. Methods: RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts. The pooled hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS), and pooled odds ratios (OR) for the overall response rate (ORR) were calculated by Review Manager 5.3. Results: The results indicated that the addition of anti-EGFR mAbs to FOLFOX regimen in RAS wild-type mCRC patients for the first-line treatment resulted in considerable improvements in PFS (HR = 0.70; 95% confidence interval [CI]: 0.59–0.82; P < .0001), OS (HR = 0.79; 95%CI: 0.67–0.92; P = .003), and ORR (OR = 2.56; 95% CI: 1.77–3.70; P < .00001) compared with chemotherapy alone. However, in RAS/BRAF wild patients, no significant differences were observed when anti-EGFR mAb was added to FLOX or XELOX regimen compared with chemotherapy alone with regard to OS and PFS, whereas FOLFOX+anti-EGFR mAb showed a marked superior OS and PFS (OS, HR = 0.77; 95% CI: 0.61–0.98; P = .03; PFS, HR = 0.68; 95% CI: 0.57–0.82; P < .00001). A meta-analysis including TAILOR and PRIME study suggests that primary tumor location (PTL) predicted a survival benefit when adding the EGFR antibody to FOLFOX regimen in RAS-wild mCRC patients (OS, HR for left-sided: 0.71; 95% CI: 0.59–0.85; P = .0002 and HR for right-sided: 0.90; 95% CI: 0.65–1.25; P = .53). However, the HR for PFS and ORR still suggests a benefit from the addition of anti-EGFR mAb in right-sided mCRC patients. Conclusion: So these results suggest anti-EGFR mAb and oxaliplatin are good partners in the FOLFOX regimen. The addition of EGFR antibody to FOLFOX markedly improved efficacy in RAS-wild patients with left-sided mCRC. In RAS/BRAF-wild patients, the efficacy is similar. For patients with right-sided tumor, a benefit showing a trendency in favor of anti-EGFR mAb can still seen. The molecular characteristics behind the tumor location need to be more explored urgently.
影响因子：
24.5
作者：
Yamauchi M;Lochhead P;Morikawa T;Huttenhower C;Chan AT;Giovannucci E;Fuchs C;Ogino S
通讯作者：
Ogino S
影响因子：
11.2
作者：
Kopetz S;Lesslie DP;Dallas NA;Park SI;Johnson M;Parikh NU;Kim MP;Abbruzzese JL;Ellis LM;Chandra J;Gallick GE
通讯作者：
Gallick GE