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Meta-Analysis
. 2013 Sep;76(3):348-57.
doi: 10.1111/bcp.12149.

Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis

Wei-Xiang Qi  1 , Ai-Na He, Zan Shen, Yang Yao
Affiliations
Meta-Analysis

Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis

Wei-Xiang Qi et al. Br J Clin Pharmacol. 2013 Sep.

Abstract

Aims: To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Methods: Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.

Results: A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR 1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34).

Conclusions: While sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.

Keywords: axitinib; hypertension; meta-analysis; tyrosine kinase inhibitor.

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Figures

Figure 1
Figure 1
Flow chart of trial selection process in the meta-analysis
Figure 2
Figure 2
Forest plot for meta-analysis of incidence of all grade hypertension in cancer patients assigned axitinib
Figure 3
Figure 3
Forest plot for meta-analysis of incidence of high grade hypertension in cancer patients assigned axitinib
Figure 4
Figure 4
Relative risk of axitinib-associated all grade hypertension vs. control from randomized controlled trials of patients with cancer
Figure 5
Figure 5
Relative risk of axitinib-associated high grade hypertension vs. control from randomized controlled trials of patients with cancer
See this image and copyright information in PMC

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