Safety and efficacy of EFGR and VEGF signaling pathway inhibition therapy in patients with colorectal cancer: a meta-analysis*

Abstract

Abstract 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.