FDA Approves Axitinib for Advanced Renal Cell Cancer

Roxanne Nelson


January 27, 2012

January 27, 2012 — The US Food and Drug Administration (FDA) has approved axitinib (Inlyta, Pfizer) for the treatment of advanced renal cell carcinoma (RCC) that has progressed after first-line systemic therapy.

"This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA's Center for Drug Evaluation and Research, in a statement. "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."

In the past 6 years, the treatment options for patients with advanced RCC have expanded with the approval of several new agents with 2 different modes of action. Drugs that target vascular endothelial growth-factor (VEGF) receptors include sorafenib (Nexavar, 2005), sunitinib (Sutent, 2006), pazopanib (Votrient, 2009), and the VEGF antibody bevacizumab (Avastin, 2009); temsirolimus (Torisel, 2007) and everolimus (Afinitor, 2009) target rapamycin (mTOR).

Axitinib is a small-molecule tyrosine kinase inhibitor that works on multiple targets, including VEGF receptors 1, 2, and 3.

As previously reported by Medscape Medical News, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted unanimously in December 2011 to recommend the approval of axitinib for the second-line treatment of patients with advanced RCC.

The approval was based on a single efficacy study, A4061032 (AXIS trial), of 723 patients with advanced RCC who had failed 1 previous therapy. AXIS was a randomized, controlled, open-label, multicenter phase 3 trial that compared axitinib with sorafenib as second-line systemic therapy. Patients were randomized to receive either axitinib 5 mg or sorafenib 400 mg, and the primary efficacy end point was progression-free survival.

The results showed that axitinib extended progression-free survival by 2 months more than sorafenib. Median progression-free survival was 6.7 months (95% confidence interval [CI], 6.3 to 8.4) for axitinib and 4.7 months (95% CI, 4.6 to 5.6) for sorafenib, with a hazard ratio of 0.67 (95% CI, 0.55 to 0.81). The objective response rate for axitinib was also superior to sorafenib (19.4% vs 9.4%).

"This is probably the most robust randomized trial, in that the comparator arm is an active and approved agent that is really contemporary treatment, not more historic treatment," Deborah K. Armstrong, MD, from the Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News at the time of the ODAC vote. "I think the data in the US population are compelling, and I agree, having used sorafenib before, that having something with a different toxicity profile for patients who don't tolerate sorafenib is certainly a plus."

The adverse event profile for axitinib is similar to that of other drugs in the same class. The most common adverse events (>10% in either group) were diarrhea, hypertension, fatigue, decreased appetite, and nausea. Higher rates of gastrointestinal events, fatigue, asthenia, hypertension, hypothyroidism, and dysphonia were observed with axitinib than with sorafenib. However, axitinib had lower rates of dermatologic adverse events and anemia than sorafenib.

Nonfatal serious adverse events occurred in 34.8% of patients in the axitinib group and 32.7% in the sorafenib group. More deaths occurred with axitinib than with sorafenib group, and more deaths in the axitinib group than in the sorafenib group were associated with treatment-emergent adverse events (2.5% vs 1.1%).

According to an FDA statement, patients with hypertension should have it well controlled before taking axitinib, and the drug is contraindicated in patients with untreated brain tumors or gastrointestinal bleeding.


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