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

Abstract

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.

Hemorrhagic events in cancer patients treated with aflibercept: a meta-analysis

“…We also explored the differences in incidence of hemorrhagic events between aflibercept and bevacizumab. We used bevacizumab as the control (with RR=1.0) to calculate the RR of hypertension for aflibercept [7]. A statistical test with a P value less than 0.05 was considered significant.…”

Multikinase Inhibitor-Induced Hand–Foot Skin Reaction: A Review of Clinical Presentation, Pathogenesis, and Management

“…Several MKIs are found to have multitargeting effects because of the structural homolog among adenosine triphosphate (ATP)-binding sites of kinases [13]. Sorafenib, sunitinib, pazopanib, cediranib, regorafenib, axitinib, vandetanib, cabozantinib, masitinib, and telatinib are small-molecule, anti-angiogenic inhibitors of the tyrosine kinase with multi-targeting inhibition [14][15][16][17][18][19][20][21][22][23][24][25]. Table 1 summarizes and lists in order of frequency (high to low) the types of anti-angiogenic MKIs, their therapeutic indications and targets, and the incidence of all-grade and high-grade (grade 3) HFSRs [14][15][16][17][18][20][21][22][23].…”

Current Practices in the Management of Adverse Events Associated With Targeted Therapies for Advanced Renal Cell Carcinoma: A National Survey of Oncologists

“…Furthermore, it highlights a need to train and increase non-oncology specialists adept in AE management in cancer patients. Lastly, dermatologic AEs such as rash[16] and hand-foot skin reaction (HSFR), besides being common with sunitinib, sorafenib, and axitinib (which has a higher risk of HSFR relative to pazopanib),[17-20] are correlates that may identify patients likely to benefit from treatment. [13] Thus, incorporation of dermatologists in the multidisciplinary management of RCC patients is crucial.…”