Tumor Biology

, Volume 37, Issue 5, pp 6297–6306 | Cite as

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

  • Yan Li
  • Xin-Yue Liang
  • Yi-Qi Yue
  • Lei Sheng
  • Ji-Kai Liu
  • Zhan-Yu Wang
  • Gang Chen
Original Article


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.


Anti-VEGF/VEGFR drugs Complete response Chemotherapy Meta-analysis 


Author contributions

Study concept and design: Yan Li and Gang Chen; acquisition of data: Yan Li, Yi-Qi Yue, and Lei Sheng; analysis and interpretation of data: Yan Li and Xin-Yue Liang; statistical analysis: Xin-Yue Liang and Yan Li; drafting of the manuscript: Yan Li, Lei Sheng, Xin-Yue Liang, Ji-Kai Liu, and Zhan-Yu Wang; and study supervision: Gang Chen and Yan Li.

Compliance with ethical standard

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yan Li
    • 1
  • Xin-Yue Liang
    • 2
  • Yi-Qi Yue
    • 3
  • Lei Sheng
    • 4
  • Ji-Kai Liu
    • 1
  • Zhan-Yu Wang
    • 1
  • Gang Chen
    • 1
  1. 1.Department of Urology, Jinshan HospitalFudan UniversityShanghaiChina
  2. 2.Institute of Clinical Pharmacology, Qilu HospitalShandong UniversityShandongChina
  3. 3.Department of GynecologyXuhui District Central HospitalShanghaiChina
  4. 4.Centre for Personalised Cancer Medicine, School of MedicineThe University of AdelaideAdelaideAustralia

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