SILVER SPRING, MD. – The data on the kinase inhibitor axitinib support its approval as a second-line treatment for advanced renal cell carcinoma, a Food and Drug Administration advisory panel unanimously agreed at a Dec. 7 meeting.
At the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-0 that axitinib has a favorable risk-benefit profile for treating patients with advanced renal cell carcinoma (RCC) after failure of a first-line systemic therapy, based on the results of an international, phase III, open-label, randomized, controlled study comparing treatment with axitinib to sorafenib (Nexavar). Sorafenib was approved in December 2005 as the first targeted therapy for RCC. Both sorafenib and axitinib are selective inhibitors of vascular endothelial growth factor (VEGF) and are administered orally twice a day.
The study enrolled 723 patients with advanced RCC who had failed one prior systemic treatment; their median age was 61 years, almost two-thirds were men, and about two-thirds were white. About 25% of the patients were enrolled in North America, and about half were enrolled in Europe. The median progression-free survival was 6.7 months among those treated with axitinib, compared with 4.7 months among those treated with sorafenib, a highly statistically significant difference.
However, 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. In this subgroup, the median progression-free survival was 5.6 months, compared with 1.4 months among those previously treated with sorafenib, who are more reflective of the types of patients treated in the United States.
Common adverse events associated with axitinib included diarrhea, nausea, fatigue, asthenia, hypertension, and skin reactions. Although its safety profile is comparable to that of other VEGF inhibitors, the side effect profile is slightly different. (Hypertension and hypothyroidism were more common among those treated with axitinib, while hand-foot-and-mouth syndrome, rash, and alopecia were more likely to occur among those on sorafenib.)
Panelists agreed that the overall toxicity profile of axitinib was comparable to that of sorafenib. And although panelists described the efficacy of axitinib as only marginally or modestly better than that of sorafenib, they agreed it would be useful to have another treatment option within the same class to offer patients who had experienced adverse effects with another agent.
If approved, axitinib will be marketed as Inlyta by Pfizer, and it would be the seventh targeted treatment approved for advanced RCC. Other targeted treatments for advanced RCC approved since December 2005 are the 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).
Axinitib has not been approved elsewhere and is under review in the European Union. It is also being studied in a phase III study of patients with treatment-naive and previously treated advanced RCC, and in a phase II study of patients with hepatocellular carcinoma.
The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. No panelists at this meeting were given a waiver.