The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: A systematic review of literature and meta-analysis
Protein Kinase Inhibitors
Pazopanib is a novel multikinase inhibitor that shares a similar spectrum of target receptors with sorafenib and sunitinib. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib and compare the difference in incidence between sorafenib, sunitinib, and pazopanib. Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 1,163 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.8% (95% CI: 0.7-4.6%), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased for all-grade (RR = 6.09, 95% CI: 1.11-33.36, p = 0.037) and high-grade HFSR (RR = 2.51, 95% CI: 0.12-51.9, p = 0.55). The risk of all-grade and high-grade HFSR to pazopanib was significantly lower as compared to sorafenib and sunitinib (RR = 7.5, 95% CI: 5.5-10.2, p < 0.001; RR = 5.9, 95% CI: 3.5-10.0, p < 0.001 and RR = 4.2, 95% CI: 3.0-5.7, p < 0.001; RR = 3.6, 95% CI: 2.1-6.2, p < 0.001). Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis.