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

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Summary

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.

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Acknowledgments

M.E.L. is supported by a Career Development Award from the Dermatology Foundation. We thank Dr. Allan C. Halpern for his review of this manuscript.

Source of support

Memorial Sloan-Kettering; Dermatology Foundation Career and Development Award

Disclosure statement

AF, SW and AH have nothing to disclose.

MEL is supported by a Career Development Award from the Dermatology Foundation. He has a consultant role with AstraZeneca Pharmaceuticals. He is also receiving research funding from Berg, Roche.

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  1. Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228 160 E 53rd St., New York, NY, USA

    Alyssa Fischer & Mario E. Lacouture

  2. Division of Medical Oncology, Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA

    Shenhong Wu

  3. Head and Neck Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Alan L. Ho

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Fischer, A., Wu, S., Ho, A.L. et al. The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs 31, 787–797 (2013). https://doi.org/10.1007/s10637-013-9927-x

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