Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Chengdu Fifth People's Hospital, Chengdu, Sichuan, China.
J Evid Based Med. 2019 Nov;12(4):300-312. doi: 10.1111/jebm.12360. Epub 2019 Oct 9.
To investigate the efficacy and safety of adding anti-epidermal growth factor receptor [EGFR] MoAbs to various chemotherapy regimens in patients with RAS wild-type metastasized colorectal cancer (RAS WT metastatic colorectal cancer [mCRC]) and to identify the optimal combination regimens.
We searched MEDLINE, EMBASE, and CENTRAL from the inception date to 20th May 2019. Randomized clinical trials investigating chemotherapy with or without anti-EGFR MoAbs in treatment of patients with RAS WT mCRC were included.
Eighteen studies involving 8848 participants were eligible. Comparing with oxaliplatin-based chemotherapy, adding anti-EGFR MoAbs benefited only in progression-free survival (PFS) (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.67 to 0.94), but not in overall survival (OS) (HR = 0.89, 95% CI: 0.78 to 1.02). Further sensitivity analysis indicated that adding anti-EGFR MoAbs to FOLFOLX regimen as a first-line treatment showed benefits in both PFS and OS (PFS: HR = 0.74, 95% CI: 0.64 to 0.84; OS: HR = 0.83, 95% CI: 0.73 to 0.95, respectively). Comparing with irinotecan-based chemotherapy or best supportive care, adding anti-EGFR MoAbs revealed an improvement in both PFS (HR = 0.77, 95% CI: 0.69 to 0.86; HR = 0.46, 95% CI: 0.40 to 0.54, respectively) and OS (HR = 0.89, 95% CI: 0.80 to 0.98; HR = 0.65, 95% CI: 0.54 to 0.78, respectively).
Anti-EGFR MoAbs as a monotherapy or in combination with either irinotecan-based chemotherapy or FOLFOX in patients with RAS wild-type mCRC have better response and survival outcome, whereas OS does not benefit from adding anti-EGFR MoAbs to another oxaliplatin-based regimen. Anti-EGFR MoAbs have increased the risk of adverse effects than chemotherapy alone. More high-quality randomized controlled trials for RAS wild type are necessary.
探讨表皮生长因子受体（EGFR）单克隆抗体联合各种化疗方案治疗 RAS 野生型转移性结直肠癌（RAS WT 转移性结直肠癌[mCRC]）患者的疗效和安全性，并确定最佳联合方案。
我们检索了 MEDLINE、EMBASE 和 CENTRAL 从成立日期到 2019 年 5 月 20 日的文献。纳入了研究 RAS WT mCRC 患者化疗联合或不联合抗 EGFR 单克隆抗体的随机临床试验。
纳入 18 项研究共 8848 名参与者。与奥沙利铂为基础的化疗相比，添加抗 EGFR 单克隆抗体仅在无进展生存期（PFS）方面获益（风险比[HR] 0.80，95%置信区间[CI]：0.67 至 0.94），但在总生存期（OS）方面无获益（HR 0.89，95%CI：0.78 至 1.02）。进一步的敏感性分析表明，将抗 EGFR 单克隆抗体添加到 FOLFOX 方案中作为一线治疗在 PFS 和 OS 方面均显示出获益（PFS：HR 0.74，95%CI：0.64 至 0.84；OS：HR 0.83，95%CI：0.73 至 0.95）。与伊立替康为基础的化疗或最佳支持治疗相比，添加抗 EGFR 单克隆抗体可改善 PFS（HR 0.77，95%CI：0.69 至 0.86；HR 0.46，95%CI：0.40 至 0.54）和 OS（HR 0.89，95%CI：0.80 至 0.98；HR 0.65，95%CI：0.54 至 0.78）。
抗 EGFR 单克隆抗体作为单一药物或与伊立替康为基础的化疗或 FOLFOX 联合应用于 RAS 野生型 mCRC 患者，具有更好的反应和生存结果，而 OS 并未从添加抗 EGFR 单克隆抗体到另一种奥沙利铂为基础的方案中获益。与单纯化疗相比，抗 EGFR 单克隆抗体增加了不良反应的风险。需要更多高质量的 RAS 野生型随机对照试验。
