FDA Approves Axitinib for Advanced Kidney Cancer Patients

The Pfizer drug axitinib gains FDA approval for advanced RCC

The FDA has approved axitinib (Inlyta) for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed to respond to another drug.

The FDA approved axitinib on January 27, 2012, based on the strength of a clinical trial that demonstrated an improvement in progression-free survival (PFS). The randomized, open-label, multicenter study involved 723 patients from 22 countries who had RCC and progressed despite receiving sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or a cytokine as first-line therapy. Patients were randomly assigned to receive either axitinib or sorafenib.

The axitinib arm demonstrated a median PFS of 6.7 months (95% CI, 6.3-8.6) compared with 4.7 months (95% CI, 4.6-5.6) for those receiving sorafenib. The results of the study, first published in The Lancet in December 2011, demonstrated a 33.5% improvement in PFS (hazard ratio [HR] = 0.665; 95% CI, 0.544-0.812; P <.0001).

Treatment was discontinued in 14 of 359 patients receiving axitinib and in 29 of 355 patients receiving sorafenib. The most common side effects reported were diarrhea, hypertension, and fatigue in the axitinib arm, and diarrhea, palmar-plantar erythrodysesthesia, and alopecia in the sorafenib arm. The FDA warned that patients with hypertension should have their blood pressure well-controlled before taking axitinib, and patients with untreated brain tumors or gastrointestinal bleeding should not take axitinib.

Axitinib is an oral kinase inhibitor designed to selectively inhibit vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, which have been known to promote angiogenesis and tumor progression.

“Through studying this drug we have learned that a VEGFR-targeted therapy can be effective following prior treatment options, including another VEGFR-targeted agent. This is important in helping physicians understand where these medications fit in the treatment armamentarium,” said Brian I. Rini, MD, associate professor of Medicine in the Department of Solid Tumor Oncology at the Cleveland Clinic in Ohio, lead author of the axitinib study and a consultant to Pfizer Oncology. Pfizer Inc will release the drug under its brand name Inlyta.

The FDA noted that this is the seventh drug approved for metastatic or advanced RCC since 2005. The other drugs that have been approved are sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab, and pazopanib.

“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,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement concerning the approval of axitinib.

In a statement released by the manufacturer, Pfizer noted that the drug is also being investigated in treatment-naïve and previously treated advanced RCC patients. Additionally, a randomized phase II trial is being conducted to test its efficacy in hepatocellular carcinoma (HCC).

The National Cancer Institute estimates that 64,770 new cases of kidney cancer will be diagnosed in 2012, and 13,570 people will die from the disease. Between 40% and 65% of patients whose disease progresses after receiving first-line therapy will receive some form of second-line therapy.