Axitinib is a
tyrosine kinase inhibitor of
vascular endothelial growth factor receptor 1 (VEGFR-1),
VEGFR-2, and
VEGFR-3. Based on the positive opinion from the European Medicines Agency (EMA), a marketing authorization valid throughout the European Union (EU) was issued for the treatment of advanced
renal cell carcinoma (RCC) after failure of prior treatment with
sunitinib or a
cytokine. The demonstration of clinical benefit for
axitinib was based on a phase III, randomized, open-label, multicenter study of
axitinib compared with
sorafenib in patients with advanced RCC after failure of a prior systemic first-line regimen containing one or more of the following agents:
sunitinib,
bevacizumab plus
interferon-α,
temsirolimus, or
cytokines. In the primary analysis, a 2-month increase in median progression-free survival (PFS) was observed for
axitinib compared with
sorafenib (hazard ratio [HR]: 0.665; 95% confidence interval [CI]: 0.544-0.812; p < .0001). In the subgroup of patients with a prior
cytokine-containing regimen, the increase in median PFS associated with
axitinib was 5.4 months (updated analysis, HR: 0.519; 95% CI: 0.375-0.720; p < .0001). In the subgroup of patients with prior
sunitinib treatment, the increase in median PFS was 1.4 months (updated analysis, HR: 0.736; 95% CI: 0.578-0.937; p = .0063). The analysis of overall survival showed no statistically significant survival benefit of
axitinib over
sorafenib in patients previously treated with
cytokine-containing regimens (HR: 0.813; 95% CI: 0.556-1.191) or
sunitinib (HR: 0.997; 95% CI: 0.782-1.270). The most common treatment-related adverse events associated with
axitinib included
diarrhea,
hypertension,
fatigue,
nausea, decreased appetite,
dysphonia, and palmar-plantar erythrodysesthesia. Most of these events were mild or moderate in severity. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).