| Siwen Liu,Rong Ma,Haixia Cao,Shaorong Yu,Dan Chen,Changwen Jing,Zhuo Wang,Junying Zhang,Jifeng Feng,Jianzhong Wu. Safety and efficacy of EFGR and VEGF signaling pathway inhibition therapy in patients with colorectal cancer: a meta-analysis. Oncol Transl Med, 2019, 5: 80-90. |
| 结直肠癌患者EGFR和VEGF信号通路抑制治疗的安全性和有效性-Meta分析 |
| Safety and efficacy of EFGR and VEGF signaling pathway inhibition therapy in patients with colorectal cancer: a meta-analysis |
| Received:November 21, 2018 Revised:May 07, 2019 |
| DOI：10.1007/s10330-018-0321-1 |
| 中文关键词: 结直肠癌；EGFR；VEGFR；Meta分析 |
| 英文关键词: colorectal cancer (CRC); epidermal growth factor receptor (EGFR); vascular endothelial ?growth factor (VEGF); meta-analysis |
| 基金项目:- |
| Author Name | Affiliation | E-mail | | Siwen Liu | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research ?& The Affiliated Cancer Hospital of Nanjing Medical University | siwenliu1989@126.com | | Rong Ma | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University | | | Haixia Cao | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University | | | Shaorong Yu | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research ?& The Affiliated Cancer Hospital of Nanjing Medical University | | | Dan Chen | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research ?& The Affiliated Cancer Hospital of Nanjing Medical University | | | Changwen Jing | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research ?& The Affiliated Cancer Hospital of Nanjing Medical University | | | Zhuo Wang | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University | | | Junying Zhang | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research ?& The Affiliated Cancer Hospital of Nanjing Medical University
Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University | | | Jifeng Feng* | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, | | | Jianzhong Wu* | Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, | |
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| 中文摘要: |
| 背景：结直肠癌是世界上最常见的恶性肿瘤之一，是癌症死亡的主要原因。尽管近年来在化疗方面取得了进展，但转移性结直肠癌的有效率低，预后差。表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）抑制剂是转移性结直肠癌（(mCRC)）的两种治疗方法。然而，很少有研究对比联合与单一使用靶向治疗对EFGR或VEGF抑制治疗的安全性和有效性。我们荟萃分析的目的是比较联合抑制疗法和单一使用抑制疗法对mCRC的抗肿瘤活性。
方法：检索PubMed、Medline、Cochrane图书馆、Embase和年度会议记录等相关临床试验。提取并计算总有效率（ORR）、无进展生存率（PFS）、总生存率（OS）和不良事件。
结果：纳入分析9例，包括3977例患者。联合抑制治疗与单次抑制相比，ORR提高3.7%，差异有统计学意义（HR=1.33；95%CI，1.01-1.74；P=0.04）。亚组分析显示，与VEGF抑制剂治疗相比，EGFR和VEGF抑制剂治疗的ORR改善了11.65%（OR=2.14；95%CI，1.34-3.40；P=0.001）。与化疗相比，EGFR、VEGF抑制剂和化疗治疗的ORR改善了18.08%（OR=2.21；95%CI，1.05-4.64；P=0.04）。此外，与VEGF抑制剂治疗相比，EGFR和VEGF抑制剂治疗显著改善了PFS（OR=0.82；95%CI，0.69-0.97；P=0.02）。与EGFR、VEGF抑制剂和化疗治疗相比，VEGF抑制剂和化疗治疗显著改善了PFS（OR=1.20；95%CI，1.11-1.30；P=0.00）。此外，与VEGF抑制剂治疗相比，EGFR和VEGF抑制剂治疗改善了OS（HR=0.78，95%CI:0.65-0.94，P=0.008）。最后，联合抑制疗法显示皮肤和粘膜效应（RR=6.45；95%CI:2.71-15.36；P<0.01）、腹泻/腹痛（RR=1.97；95%CI:1.45-2.68；P<0.01）、疲劳/乏力（RR=1.60；95%CI:1.10-2.32；P=0.01）、脱水或电解质紊乱（RR=2.78；95%CI:1.48-5.21；P<0.0）的风险明显增加。1），与单一抑制疗法相比，指甲疾病（RR=8.23；95%CI:1.52-44.57；P=0.01）和头晕/头痛（RR=3.43；95%CI:1.89-6.23；P<0.01）。。
结论：联合抑制治疗与单次抑制治疗相比，可明显改善mCRC患者的ORR，但不增加PFS和OS。与单一靶向药物相比，联合应用抗EGFR和抗VEGF药物具有疗效优势，但毒性较大。 |
| 英文摘要: |
| Objective Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)
inhibitors are two targeted therapies for metastatic colorectal cancer (mCRC). However, few studies have
focused on the safety and efficacy of combined targeted therapy against those of a single inhibition therapy
of EFGR or VEGF. This meta-analysis aimed to compare the anti-tumor activity of the combined inhibition
therapy and single inhibition therapy in patients with mCRC.
Methods We searched PubMed, Medline, the Cochrane library, Embase, and annual meeting
proceedings for relevant clinical trials. Objective response rate (ORR), progression-free survival (PFS),
overall survival (OS), and adverse events were extracted and calculated.
Results Nine trials comprising 3977 patients were selected for the analysis. The combined inhibition
therapy showed a 3.7% improvement in ORR compared with single inhibition, and this difference was
statistically significant [hazard ratio (HR) = 1.33; 95% confidence interval (CI), 1.01–1.74; P = 0.04].
Subgroup analysis showed that the combined EGFR and VEGF inhibitor therapy had an 11.65%
improvement in ORR compared with VEGF inhibitor therapy (OR = 2.14; 95% CI, 1.34–3.40; P = 0.001).
EGFR and VEGF inhibitor therapy and chemotherapy had an 18.08% improvement in ORR compared with
chemotherapy (OR = 2.21; 95% CI, 1.05–4.64; P = 0.04). Moreover, EGFR and VEGF inhibitor therapy
significantly improved PFS compared with VEGF inhibitor therapy (OR = 0.82; 95% CI, 0.69–0.97; P =
0.02). VEGF inhibitor therapy and chemotherapy significantly improved PFS compared with EGFR and
VEGF inhibitor therapy and chemotherapy (OR = 1.20; 95% CI, 1.11–1.30; P = 0.00). In addition, EGFR
and VEGF inhibitor therapy showed improved OS compared with VEGF inhibitor therapy (HR = 0.78, 95%
CI: 0.65–0.94; P = 0.008). Finally, the combined inhibition therapy showed an obviously increased risk of
cutaneous and mucosal effects (RR = 6.45; 95% CI: 2.71–15.36; P < 0.01), diarrhea/abdominal pain (RR =
1.97; 95% CI: 1.45–2.68; P < 0.01), fatigue/asthenia (RR = 1.60; 95% CI: 1.10–2.32; P = 0.01), dehydration
or electrolyte disturbance (RR = 2.78; 95% CI: 1.48–5.21; P < 0.01), nail disorder (RR = 8.23; 95% CI:
1.52–44.57; P = 0.01), and dizziness/headache (RR = 3.43; 95% CI: 1.89–6.23; P < 0.01) compared with
single inhibition therapy.
Conclusion Compared with single inhibition therapy, the combined inhibition therapy significantly
improved ORR, PFS, and OS in the treatment of mCRC patients. Compared with a single-targeted agent,
the combined therapy of anti-EGFR and anti-VEGF drug provided an efficacy advantage, although it led to
greater toxicity. |
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