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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

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Tumor Biology

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.

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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.

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Authors and Affiliations

  1. Department of Urology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201500, China

    Yan Li, Ji-Kai Liu, Zhan-Yu Wang & Gang Chen

  2. Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Shandong, China

    Xin-Yue Liang

  3. Department of Gynecology, Xuhui District Central Hospital, Shanghai, China

    Yi-Qi Yue

  4. Centre for Personalised Cancer Medicine, School of Medicine, The University of Adelaide, Adelaide, Australia

    Lei Sheng

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  1. Yan Li
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Li, Y., Liang, XY., Yue, YQ. et al. 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. Tumor Biol. 37, 6297–6306 (2016). https://doi.org/10.1007/s13277-015-4493-9

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