Sutent (sunitinib malate) - 4 indications

Scroll down for information on each indication:

• for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors; approved January 2006
• for the treatment of pancreatic neuroendocrine tumors; approved May 2011
• the adjuvant treatment for patients at a high risk of recurrent renal cell carcinoma following nephrectomy; approved November 2017

General Information

Sutent (sunitinib malate) is an orally-available small-molecule multiple receptor tyrosine kinase inhibitor. 

Sutent is specifically indicated for the following indications:

• for the treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate
• for the treatment of adult patients with advanced renal cell carcinoma (RCC)
• for the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy
• for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease

Sutent is supplied as a hard gelatin capsule for oral administration. Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Sutent (sunitinib malate) is designed to inhibit multiple receptor tyrosine kinases, including platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). A number of these kinases have been implicated in tumor growth, pathologic angiogenesis, and cancer metastasis.

Side Effects

Adverse events associated with the use of Sutent (all indications) may include, but are not limited to, the following:

• fatigue/asthenia
• diarrhea
• nausea
• decreased appetite/anorexia
• stomatitis/mucositis
• vomiting
• abdominal pain
• hypertension
• bleeding
• hand-foot syndrome
• dysgeusia/altered taste
• dyspepsia
• thrombocytopenia

The Sutent drug label comes with the following Black Box Warning: HEPATOTOXICITY Hepatotoxicity may be severe, and in some cases fatal. Monitor hepatic function and interrupt, dose reduce, or discontinue Sutent as recommended.

Indication 1 - advanced renal cell carcinoma

approved January 2006

Dosing/Administration

The recommended dosage is 50 mg taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) until disease progression or unacceptable toxicity. Sutent may be taken with or without food.

Clinical Trial Results

Approval of single-agent Sutent for the treatment of RCC was based on a pair of single-arm, multi-center studies.

Study 1
This trial enrolled 106 patients who had failed prior cytokine therapy (as defined by radiographic evidence of disease progression (RECIST or WHO criteria) within 9 months of completion of a cytokine regimen). The trial was designed to investigate the objective response rate of Sutent therapy. Subjects received daily doses of 50 mg Sutent on the 4-weeks-on/2-weeks-off schedule until evidence of disease progression or eligibility for withdrawal was met. Sutent was shown to produce objective tumor responses (Partial responses) in 25.5% of subjects (n=27), with a median duration of response to date of 27.1 weeks (these data were immature at the time of approval, as 41.5% of subjects remained on protocol without evidence of progression to date).

Study 2
Study 2 utilized a similar design to trial 1, treating 63 RCC patients failing cytokine therapy (as defined by evidence of disease progression or unacceptable treatment-related toxicity) on the 50 mg, 4/2 regimen. This study was also designed to investigate objective response rate and duration of response. In this study, Sutent produced partial tumor responses in 36.5% of subjects (n=23), with a median response duration of 54 weeks. At the time of approval, 11 patients remained on protocol, with ongoing disease responses.

Indication 2 - gastrointestinal stromal tumors

approved January 2006

Dosing/Administration

The recommended dosage is 50 mg taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) until disease progression or unacceptable toxicity. Sutent may be taken with or without food.

Clinical Trial Results

Approval of Sutent for the treatment of GIST was based on two studies, dubbed Study A and Study B.

Study A
This two-arm, international, randomized, double-blind, placebo-controlled study enrolled 312 patients, who received either 50 mg Sutent (n=207) or placebo (n=105) once daily for 4 weeks, followed by 2 weeks off, until evidence of disease progression was observed. Sutent was shown to significantly increase median time to tumor progression, to 27.3 weeks, vs. 6.4 weeks for placebo. Secondary efficacy was also established, with the drug producing progression free survival (24.1 weeks, vs. 6.0 weeks) and an objective response rate (6.8% vs. 0%) superior to placebo.

Study B
This open-label, multi-center, single-arm, dose-escalation study was designed to investigate the objective tumor response rate for Sutent therapy. The trial enrolled 55 subjects, who received 50 mg Sutent once daily on the 4-weeks on/2-weeks off schedule. Trial data yielded confirmed partial responses in 5 subjects, a 9.1% objective response rate.

Indication 3 - pancreatic neuroendocrine tumors

approved May 2011

Dosing/Administration

The recommended dosage is 37.5 mg taken orally once daily until disease progression or unacceptable toxicity. Sutent may be taken with or without food.

Clinical Trial Results

The FDA approval of Sutent for pancreatic neuroendocrine tumors was based on a multi-center, international, randomized, double-blind placebo-controlled study in 171 subjects with unresectable pNET. The subjects were randomized to either 37.5 mg Sutent or placebo once daily without a scheduled off-treatment period. The primary endpoint was Progression-Free Survival (PFS). The median PFS in the Sutent arm was 10.2 months versus 5.4 months in the placebo arm. The Objective Response Rate was 9.3% versus 0%, respectively.

Indication 4 - adjuvant treatment for high risk of recurrent renal cell carcinoma following nephrectomy

approved November 2017

Dosing/Administration

The recommended dosage for the adjuvant treatment of RCC is 50 mg taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2), for nine 6-week cycles. Sutent may be taken with or without food.

Clinical Trial Results

FDA approval was based on S-TRAC, a multi-center, international, randomized, double-blind, placebo-controlled, trial in patients with high risk of recurrent RCC following nephrectomy. Patients were required to have clear cell histology and high risk of recurrence defined as ≥T3 and/or N+ tumors. Patients (n=615) were randomized 1:1 to receive either 50 mg Sutent once daily on Schedule 4/2 or placebo. Patients were treated for 9 cycles (approximately 1 year), or until disease recurrence, unacceptable toxicity, or withdrawal of consent. The major efficacy outcome measure was disease-free survival (DFS) in patients receiving Sutent versus placebo. After five years, 59.3 percent of patients treated with Sutent had not experienced cancer recurrence or death compared with 51.3 percent of patients receiving placebo.