FDA Approves Adjuvant Therapy for High-Risk Renal Cell Carcinoma

The new indication is for adjuvant treatment in patients at high risk of disease recurrence after surgery

The US Food and Drug Administration (FDA) has approved sunitinib malate (Sutent, Pfizer Inc) for the adjuvant treatment of adult renal cell carcinoma patients at high risk of recurrence following nephrectomy.

It is the first approved therapy “to potentially reduce cancer recurrence” in such patients, said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, in a press release from the agency.

In 2006, the FDA initially approved sunitinib, a kinase inhibitor, for treating gastrointestinal stromal tumors and advanced renal cell carcinoma.

“Some patients who have undergone surgery for locally advanced renal cell carcinoma are at a high risk of recurrence and often fear their disease recurring,” said study investigator Daniel George, MD, of Duke University Medical Center in Durham, North Carolina, in a press release. “This adjuvant therapy is the first of its kind, and a remarkable clinical development for these patients who before today, have been restricted to a wait-and-see approach.”

The FDA approval was based on the S-TRAC trial, a multicenter, international, double-blind, placebo-controlled, phase III trial of sunitinib in 615 renal cell carcinoma patients with a high risk of recurrence following nephrectomy. Patients were randomized 1:1 to receive 50 mg sunitinib-or placebo-once daily for 4 weeks, followed by 2 weeks off.

Median disease-free survival for patients taking sunitinib was 6.8 years (95% CI, 5.8–not reached) compared with 5.6 years (95% CI, 3.8–6.6) for patients receiving placebo (hazard ratio, 0.76; 95% CI, 0.59–0.98; P = .03).

Five years after treatment with sunitinib, the disease-free survival rate was 59.3%, compared with 51.3% for patients receiving placebo.

The results were published last year in the New England Journal of Medicine.

No new safety signals were identified in the S-TRAC trial, according to data presented to the FDA. The most common adverse events, occurring in 20% or more patients, included mucositis/stomatitis (61%), fatigue/asthenia (57%), diarrhea (57%), hand-foot syndrome (50%), hypertension (39%), altered taste (38%), nausea (24%), abdominal pain (25%), hypothyroidism or increased thyroid-stimulating hormone (24%), bleeding events (24%), and hair color changes (22%).

The prescribing information for sunitinib contains a boxed warning about the risk of hepatoxicity, which may result in liver failure or death.

Other warnings and precautions include thyroid dysfunction, impaired wound healing, hypertension, cardiovascular events, embryo-fetal toxicity, and hemorrhagic events.