Axitinib is a
tyrosine kinase inhibitor of
vascular endothelial growth factor receptor,
platelet-derived growth factor receptor-α, and c-kit. Phase I studies demonstrated 5 mg twice daily as the recommended starting dose with notable effects seen in
renal cell carcinoma, an observation confirmed in Phase II trials. The trial of comparative effectivess of
axitinib versus
sorafenib in advanced
renal cell carcinoma (AXIS) was an international randomized Phase III study designed for registration purposes, compared
axitinib to
sunitinib. This trial randomized 723 patients with metastatic
kidney cancer to
axitinib or
sunitinib in the second-line setting and demonstrated a median progression-free survival of 6.7 months for
axitinib versus 4.7 months for
sorafenib (P<0.0001). Clinical benefit was detected regardless of prior
therapy, but no overall survival benefit has been observed.
Axitinib is well tolerated without a significant effect on quality of life. The most common grade 3 toxicities are
hypertension (16%),
diarrhea (11%), and
fatigue (11%), with other notable side effects being
anorexia,
nausea,
hand-foot syndrome, and
rash. Patients who developed diastolic blood pressure >90 mmHg were noted to have significantly longer median overall survival and overall response rates when compared to normotensive patients. Therefore, the manufacturer recommends escalating the twice-daily dose to 7 mg and 10 mg, as tolerated, if there is no significant increase in blood pressure on treatment. Currently,
axitinib is approved for use in the second-line setting for patients with metastatic
renal cell carcinoma. Research is ongoing in other disease settings.