贝伐单抗与表皮生长因子受体抑制剂治疗野生型转移性结直肠癌的疗效：一项荟萃分析。

Efficacy of bevacizumab versus epidermal growth factor receptor inhibitors for wild-type metastatic colorectal cancer: a meta-analysis.

作者信息

Jiang Wei, Yu Qitao, Ning Ruiling, Zhao Wenhua, Wei Changyuan

机构信息

Department of Medical Oncology, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People's Republic of China.

Department of Breast Surgery, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People's Republic of China,

出版信息

Onco Targets Ther. 2018 Jul 24;11:4271-4281. doi: 10.2147/OTT.S168695. eCollection 2018.

BACKGROUND

Results from several prospective clinical trials comparing anti-epidermal growth factor receptor (EGFR) therapy and anti-vascular endothelial growth factor (VEGF) therapy plus chemotherapy for wild-type metastatic colorectal cancer (mCRC) have been inconsistent. This meta-analysis aims to investigate the optimal choice for these target agents.

METHODS

We searched for clinical trials in both electronic databases from inception until January 2018 and recent conference abstracts to identify prospective clinical studies comparing the efficacy of a VEGF inhibitor (bevacizumab) versus EGFR inhibitors (cetuximab or panitumumab) on wild-type (including its subset ) mCRC. All analyses were conducted using RevMan 5.3 software.

RESULTS

A total of 5 studies were included. EGFR inhibitors were associated with a significant benefit in terms of overall survival (OS) compared with VEGF inhibitors in wild-type or wild-type populations, with hazard ratios (HRs) equal to 0.86 (95% CI: 0.78, 0.95; =0.003) and 0.83 (95% CI: 0.72, 0.95; =0.007), respectively. This survival benefit was limited to the first-line setting. No difference was found for progression-free survival (PFS), whereas the objective response rate (ORR) was significantly increased in the wild-type population (OR: 0.64; 95% CI: 0.50, 0.82; =0.0004). No difference in OS was noted between EGFR inhibitors versus a VEGF inhibitor plus the FOLFIRI regimen, whereas superior survival was noted for EGFR inhibitors plus the mFOLFOX6 regimen versus a VEGF inhibitor (HR: 0.75; 95% CI: 0.57, 0.98; =0.04). PFS was significantly prolonged (HR: 1.48; 95% CI: 1.14, 1.92; =0.003), whereas a trend favoring OS (HR: 1.23; 95% CI: 0.93, 1.63; =0.14) was noted for a VEGF inhibitor in patients with right-sided tumors, with no difference in the ORR (OR: 0.85; 95% CI: 0.52, 1.38; =0.51). However, left-sided tumors exhibited superior OS (HR: 0.71; 95% CI: 0.59, 0.85; =0.0002), PFS (HR: 0.84; 95% CI: 0.72, 0.98; =0.03), and ORR (OR: 0.66; 95% CI: 0.48, 0.92; =0.01) for EGFR inhibitors.

CONCLUSION

This meta-analysis suggests the superiority of anti-EGFR therapy compared with anti-VEGF therapy for mCRC with wild-type . Primary tumor location should be taken into account in target drug selection. Further research is still needed to confirm which inhibitor may be a better choice when combined with different chemotherapy regimens.

背景

多项前瞻性临床试验比较了抗表皮生长因子受体（EGFR）疗法与抗血管内皮生长因子（VEGF）疗法联合化疗用于野生型转移性结直肠癌（mCRC）的疗效，结果并不一致。本荟萃分析旨在探究这些靶向药物的最佳选择。

方法

我们检索了从数据库建立至2018年1月的电子数据库及近期会议摘要，以确定比较VEGF抑制剂（贝伐单抗）与EGFR抑制剂（西妥昔单抗或帕尼单抗）对野生型（包括其亚组）mCRC疗效的前瞻性临床研究。所有分析均使用RevMan 5.3软件进行。

结果

共纳入5项研究。在野生型或野生型人群中，与VEGF抑制剂相比，EGFR抑制剂在总生存期（OS）方面具有显著优势，风险比（HR）分别为0.86（95%CI：0.78，0.95；P = 0.003）和0.83（95%CI：0.72，0.95；P = 0.007）。这种生存获益仅限于一线治疗。无进展生存期（PFS）无差异，而野生型人群的客观缓解率（ORR）显著提高（OR：0.64；95%CI：0.50，0.82；P = 0.0004）。EGFR抑制剂与VEGF抑制剂加FOLFIRI方案相比，OS无差异，而EGFR抑制剂加mFOLFOX6方案与VEGF抑制剂相比，生存期更优（HR：0.75；95%CI：0.57，0.98；P = 0.04）。右侧肿瘤患者中，VEGF抑制剂使PFS显著延长（HR：1.48；95%CI：1.14，1.92；P = 0.003），OS有改善趋势（HR：1.23；95%CI：0.93，1.63；P = 0.14），ORR无差异（OR：0.85；95%CI：0.52，1.38；P = 0.51）。然而，左侧肿瘤患者中，EGFR抑制剂的OS（HR：0.71；95%CI：0.59，0.85；P = 0.0002）、PFS（HR：0.84；95%CI：0.72，0.98；P = 0.03）和ORR（OR：0.66；95%CI：0.48，0.92；P = 0.01）更优。