title: 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.
abstract: 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.
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201500, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Liang
authors.affiliation: Department of Gynecology, Xuhui District Central Hospital, Shanghai, China.
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Yue
authors.affiliation: Centre for Personalised Cancer Medicine, School of Medicine, The University of Adelaide, Adelaide, Australia.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201500, China.
authors.forename: Ji-Kai
authors.initials: JK
authors.lastname: Liu
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201500, China.
authors.forename: Zhan-Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201500, China. chgan305@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab / Q000008:administration & dosage; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Anti-VEGF/VEGFR drugs; Chemotherapy; Complete response; Meta-analysis