Second oral agent is approved for advanced RCC

March 1, 2006

New York--The FDA has granted approval of oral sunitinib malate (Sutent), a multi-targeted receptor tyrosine kinase inhibitor, for the treatment of advanced renal cell carcinoma. The approval came after a priority review and was based on results from two phase II clinical trials dem-onstrating impressive drug activity measured by high partial response rates and delay to disease progression. It marks the second FDA approval of a drug for advanced RCC in as many months.

In an initial open-label, uncontrolled study, 63 patients with metastatic renal cell carcinoma who had failed first-line cytokine therapy received sunitinib for a median of 9 months (range, <1 to >24 months).

"Sunitinib is a novel compound and an important new therapeutic option that offers the ease of oral administration, favorable tolerability, and a high level of antitumor activity in a disease setting for which there have not been effective treatments," said Robert J. Motzer, MD, an investigator in the sunitinib clinical trials and an attending physician, division of genitourinary oncology, Memorial Sloan-Kettering Cancer Center, New York.

Dr. Motzer is also the lead author of a recently published article reporting the results of the initial phase II study (J Clin Oncol 2006; 24:16-24).

"Current options for metastatic renal cancer include high-dose interleukin-2 or subcutaneous interferon-alfa. However, those interventions have been associated with less than a 5% partial response rate when given as second-line treatment, and other second-line treatments have been associated with similarly poor results, with a partial response rate of only 4% and a median time to progression of only about 2.5 months," Dr. Motzer explained.

In the phase II studies, patients received once-daily treatment with sunitinib in 6-week cycles of 4 weeks on and 2 weeks off. Treatment was initiated at a dose of 50 mg/day, and the protocol allowed titration up or down in 12.5 mg/day increments based on treatment-related toxicity. Dose escalation was possible in a small proportion of patients, but use of a dose higher than 50 mg/day was not associated with evidence of greater therapeutic benefit.

Treatment-related toxicity necessitated dosage reductions in about one-third of patients. Over all, the most common side effects associated with sunitinib were fatigue, gastrointestinal-related adverse events, and stomatitis. However, those reactions were generally mild to moderate in severity and improved with dosage reduction or during the off period in the treatment cycle.

Sunitinib dosage was reduced most often because of asymptomatic hyperlipasemia or hyperamylasemia and fatigue. In addition, sunitinib caused some transient lowering of blood cell counts, but that effect was not associated with bleeding events or infection. Several patients discontinued treatment because of a decline in cardiac ejection fraction.