The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis

Axitinib is a potent, selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We have performed a systematic analysis to investigate the risk of hand-foot skin reaction (HFSR) to axitinib and compare the differences in incidences between sorafenib, sunitinib, pazopanib and axitinib. Relevant studies were identified from PubMed (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with axitinib monotherapy at a starting dose of 5 mg orally twice daily. Incidence, relative risk (RR), and 95 % confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. A total of 984 patients from 6 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 29.2 % (95 % CI: 14.0-51.1 %) and 9.6 % (95 % CI: 4.2-20.7 %), respectively. The relative risks of all-grade and high-grade HFSR to axitinib compared to sorafenib were decreased for all-grade (RR = 0.54, 95 % CI: 0.44-0.65, p < 0.001) and high-grade HFSR (RR = 0.31, 95 % CI: 0.19-0.52, p < 0.001). The risk of all-grade and high-grade HFSR to axitinib, sunitinib and sorafenib was significantly higher as compared to pazopanib (RR = 6.49, 95 % CI: 4.65-9.05, p < 0.001; RR = 6.40, 95 % CI: 3.60-11.37, p < 0.001, and RR = 4.20, 95 % CI: 3.07-5.75, p < 0.001; RR = 3.67, 95 % CI: 2.15-6.24, p < 0.001, and RR = 7.51, 95 % CI: 5.5-10.3, p < 0.001; RR = 5.93, 95 % CI: 3.5-10.0, p < 0.001, respectively). Similar to sorafenib and sunitinib, axitinib is associated with a significant risk of HFSR, despite having an increased specificity for VEGF receptors. These findings underscore the importance of supportive dermatologic care in patients treated with axitinib, in order to maintain quality of life, adherence, and persistence to therapy.