FDA converts approval from accelerated to regular for sunitinib malate (Sutent) for the treatment of advanced renal cell carcinoma

On February 2, 2007, the U. S. Food and Drug Administration converted the approval of sunitinib malate (SUTENT, Pfizer, Inc.) for the treatment of advanced renal cell carcinoma from accelerated approval to regular approval following confirmation of an improvement in progression-free survival (PFS).  Sunitinib was originally approved, under the accelerated approval program, for use in this indication in January, 2006 based on partial response rates and response duration.  A further description of the FDA accelerated approval regulations is at http://www.fda.gov/cder/guidance/5645fnl.htm.

Efficacy was demonstrated in a multi-center, international randomized trial enrolling 750 patients with treatment-naïve metastatic renal cell carcinoma.  Patients were randomized to receive either sunitinib or interferon-α (IFN-α).  Sunitinib was administered at a starting dose of 50 mg orally once daily for 4 weeks, followed by two weeks off treatment.  IFN-α was given subcutaneously on three nonconsecutive days/week at a starting dose of 3 MU per dose during the first week, 6 MU per dose the second week and 9 MU per dose thereafter.

 

The two treatment arms were balanced for baseline demographic characteristics.  Patients were required to have a component of clear cell histology.  Ninety percent had prior nephrectomy.  The median number of disease sites was two.  Common metastatic sites included lung, lymph nodes, bone and liver.

 

Efficacy data were based on an interim PFS analysis by an independent data review committee.  There were 96 events (25.6%) of progression/death on sunitinib compared with 154 events (41.1%) on IFN-α.  Median PFS was 47.3 weeks (95% CI 42.6, 50.7) for sunitinib-treated patients and 22.0 weeks (95% CI 16.4, 24.0) for patients treated with IFN; the hazard ratio was 0.415 (95% CI .320, 0.539, p<0.000001).  Objective response rate on the sunitinib arm was 27.5% (95% CI 23.0%, 32.3%) vs. 5.3% (95% CI 3.3%, 8.1%) on IFN-α.  Overall survival data were not mature at the time of the second interim analysis.

 

Treatment-emergent adverse events occurring more commonly on sunitinib included GI events (diarrhea, nausea, mucositis, vomiting, dyspepsia, abdominal pain, gastroesophageal reflux, oral pain, glossodynia and flatulence), bleeding, hypertension, dermatologic events (rash, skin discoloration, dry skin, and hair color changes), hand-foot syndrome, limb pain, decreases in cardiac ejection fraction, and peripheral edema.  Treatment-emergent hypothyroidism was also more common in patients receiving sunitinib.

 

Grade 3/4 adverse events more common on sunitinib included hypertension, diarrhea, hand-foot syndrome, nausea, vomiting, mucositis, and bleeding.

 

Grade 3/4 laboratory abnormalities more common in sunitinib-treated patients included hematologic abnormalities (neutropenia, thrombocytopenia, and leucopenia), increased lipase, increased amylase, hyponatremia, hyperuricemia, and hyperbilirubinemia.

 

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2007/021968s005lbl.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by phone at 1-800-FDA-1088; by facsimile 1-800-FDA-0178 by mail using the Form 3500 at http://www.fda.gov/medwatch.index.html.

For further information related to oncology drug approvals, regulatory information, and other oncology resources, please refer to the FDA “Oncology Tools” website at www.fda.gov/cder/cancer.

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