Abstract
Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been investigated in several studies for the treatment of advanced gastric cancer (GC). In the present study, we aimed to evaluate the efficacy and safety of angiogenesis inhibitors in advanced GC. We searched published randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for the treatment of GC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HR) and corresponding 95 % confidence intervals (CIs). In addition, risk ratios (RR) and corresponding 95 % CIs were pooled for objective response rate (ORR), disease control rate (DCR), and risk of adverse events (AEs). Ten RCTs involving 2786 patients were included. Compared with non-angiogenesis inhibitor-containing regimens, angiogenesis inhibitor-containing regimens resulted in a significant improvement in OS (HR 0.80, 95 % CI 0.69–0.93, P = 0.004), prolonged PFS (HR 0.66, 95 % CI 0.51–0.86, P = 0.002), and superior ORR (RR 1.34, 95 % CI 1.09–1.65, P = 0.005) and DCR (RR 1.37, 95 % CI 1.17–1.61, P = 0.0001). Angiogenesis inhibitors were associated with a greater number of AEs, but most of these were predictable and manageable. However, hand-foot syndrome, diarrhea, and gastrointestinal (GI) perforation were significantly increased in patients treated with angiogenesis inhibitors. In summary, angiogenesis inhibitor-containing regimens were superior to non-angiogenesis inhibitor-containing regimens in terms of OS, PFS, RR, and DCR in patients with advanced GC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0340-8) contains supplementary material, which is available to authorized users.
Highlights
Gastric cancer (GC) is the fifth most common malignancy worldwide and is the third leading cause of cancer deaths in both sexes, accounting for 723,000 deaths (8.8 % of the total), with the highest estimated mortality rates in East Asia and the lowest in North America [1,2,3]
Two studies [25, 26] enrolled patients who were treated with anti-vascular endothelial growth factor (VEGF)-based drugs, five studies [9,10,11, 13, 27] enrolled patients who were treated with anti-VEGF receptor (VEGFR)-2 agents, and three trials [18, 23, 24] enrolled patients who were treated with inhibitors of multiple tyrosine kinases
The results show that angiogenesis inhibitors increased progression-free survival (PFS) in both Asian patients (HR 0.62, 95 % confidence intervals (CIs) 0.42–0.93, P = 0.02, Additional file 2: Figure S1C) and non- Asian patients (HR 0.61, 95 % CI 0.53–0.69, P < 0.00001, Additional file 2: Figure S1D) but only improved overall survival (OS) in non-Asian patients (HR 0.82, 95 % CI 0.70–0.95, P < 0.007, Additional file 2: Figure S1B)
Summary
Gastric cancer (GC) is the fifth most common malignancy worldwide and is the third leading cause of cancer deaths in both sexes, accounting for 723,000 deaths (8.8 % of the total), with the highest estimated mortality rates in East Asia and the lowest in North America [1,2,3]. Despite a significant decline in incidence worldwide over the last few decades, most GC patients are diagnosed at an advanced stage with 5-year overall survival (OS) rates for all stages combined generally below 30 %. Palliative systemic chemotherapy usually represented by a Recent studies have shown that angiogenesis in GC is a key step in metastasis. It has been confirmed that the vascular endothelial growth factor (VEGF) family is a crucial mediator of angiogenesis [4].
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