Does the addition of drugs targeting the vascular endothelial growth factor pathway to first-line chemotherapy increase complete response? A meta-analysis of randomized clinical trials

• Published in: Tumor biology Vol. 37; no. 5; pp. 6297 - 6306
• Main Authors: Li, Yan, Liang, Xin-Yue, Yue, Yi-Qi, Sheng, Lei, Liu, Ji-Kai, Wang, Zhan-Yu, Chen, Gang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2016; Springer Nature B.V
• Subjects: Angiogenesis Inhibitors - administration & dosage; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab - administration & dosage; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Chemotherapy; Clinical trials; Growth factors; Humans; Meta-analysis; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Original Article; Protein Kinase Inhibitors - administration & dosage; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-1 - genetics; Chemotherapy; Anti-VEGF/VEGFR drugs; Complete response; Meta-analysis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-4493-9

Drugs targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling (anti-VEGF/VEGFR drugs) are the most validated anti-angiogenic strategies for cancer treatment. Complete response (CR) is a rare event in cancer patients receiving chemotherapy. A meta-analysis was conducted to determine whether adding anti-VEGF/VEGFR drugs to chemotherapy can further increase the chance of CR in the first-line therapy. Relevant databases were systematically searched for the period 2000–2015. Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 12,453 patients from 28 randomized controlled trials were included. The overall incidence of CR in patients treated with anti-VEGF/VEGFR drugs plus chemotherapy was 1.5 % (95 % CI, 1.0–2.0 %) compared to 1.1 % (95 % CI, 0.7–1.4 %) in the chemotherapy-alone arm. Adding anti-VEGF/VEGFR drugs was associated with significant improvement of CR (RR, 1.52, 95 % CI, 1.18–1.95, P  = 0.001). When stratified by drug type, adding VEGFR tyrosin kinase inhibitors (TKIs) did not increase the chance of CR (RR, 0.87, 95 % CI, 0.51–1.49; P  = 0.614). The addition of bevacizumab with 7.5 mg/kg every 3 weeks, but not 15 mg/kg every 3 weeks, significantly improves the CR (7.5 mg, RR, 2.43, 95 % CI, 1.64–3.60, P  = 0.000; 15 mg, RR, 1.07, 95 % CI, 0.63–1.81, P  = 0.799). In subgroup analysis, a significant improvement of CR by the addition of anti-VEGF/VEGFR drugs was observed in patients with colorectal cancer (RR, 2.10, 95 % CI 1.21–3.63, P  = 0.008), ovarian cancer (RR, 3.07; 95 % CI, 1.68–5.62, P  = 0.000), and patients who are treated with platinum-based regimens (RR, 1.78, 95 % CI, 1.23–2.59, P  = 0.002). Low-dose bevacizumab, rather than VEGFR TKIs or high-dose bevacizumab, can increase the chance of CR in patients receiving chemotherapy.