Axitinib, a kinase inhibitor, received approval for the treatment of advanced renal cell cancer and is the seventh drug approved for metastatic or advanced kidney cell cancer since 2005, the Food and Drug Administration announced on Jan. 27.
"Collectively, this unprecedented level of drug development within this time period has significantly altered the treatment paradigm of metastatic kidney cancer, and offers patients multiple treatment options," Dr. Richard Pazdur, director of the FDA’s Office of Hematology and Oncology Products, said in the FDA statement.
The approved indication for axitinib is for the treatment of advanced renal cell carcinoma (RCC) "after failure of one prior systemic therapy." Approval was based on a single randomized, open-label, multicenter clinical study of 723 patients whose disease had progressed on or after treatment with one prior systemic therapy, according to the FDA statement.
In the study, median progression-free survival was 6.7 months among those treated with axitinib, compared with 4.7 months for those treated with sorafenib, a standard treatment for the disease. Both sorafenib (Nexavar), approved in 2005, and axitinib are selective inhibitors of vascular endothelial growth factor (VEGF) and are administered orally twice a day.
Axitinib has an antiangiogenic effect. It inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptors (PDGF), according to the National Cancer Institute.
Axitinib will be marketed as Inlyta by Pfizer. Axitinib inhibits receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.
The other targeted treatments for advanced RCC that have been approved are VEGF-receptor inhibitors sunitinib (Sutent) and pazopanib (Votrient), the anti-VEGF antibody bevacizumab (Avastin), and the mammalian target of rapamycin (mTOR) inhibitors temsirolimus (Torisel) and everolimus (Afinitor).
The most common side effects reported to occur among more than 20% of patients treated with axitinib included diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome (palmar-plantar erythrodysesthesia), weight loss, vomiting, asthenia, and constipation.
The warnings and precautions section of the label advises that blood pressure should be well controlled before patients start treatment with axitinib and should be monitored during treatment.
At a meeting on Dec. 7, 2011, the FDA’s Oncologic Drugs Advisory Committee unanimously recommended that axitinib be approved for advanced RCC, based on the study findings, although the efficacy findings were driven primarily by the results among patients previously treated with cytokines, a population less likely to be seen in the United States.