Huan Sun1, Yonghong Li1, Yana Su1, Xinyu Wu2, Xiaoqin Zhou3, Jin Han4, Jing Li1. 1. Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. 2. Chengdu Fifth People's Hospital, Chengdu, Sichuan, China. 3. Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, Sichuan, China. 4. School of Life Science and Technology, Shanghai Jiaotong University, Shanghai, China.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.