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Hand-foot skin reaction, an anticipated dermatologic toxicity to pazopanib, with an unexpected low incidence: A systematic review of literature and meta-analysis.

365 Background: Pazopanib is a novel multikinase inhibitor that has been approved for the treatment of advanced renal cell carcinoma (RCC). It shares a similar spectrum of target receptors with sorafenib and sunitinib, including VEGFR, PDGFR, and c-kit tyrosine kinases. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib. Exploring the differences in the incidence of HFSR between sorafenib, sunitinib, and pazopanib may offer additional insights into underlying mechanisms of this toxicity.


METHODS
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.


RESULTS
A total of 942 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 1.5% (95% CI: 0.7-3.1 %), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased, reaching statistical significance for all-grade (RR=6.05, 95% CI: 1.11-33.12, p=0.038), but not for high-grade (RR=2.51, 95% CI: 0.12-51.9, p=0.55). The incidence of all-grade HFSR was significantly higher in patients with RCC as compared to patients with non-RCC malignancies (7.8% vs. 2.4%, p value=0.015).


CONCLUSIONS
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. [Table: see text].