Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma.

Abstract

PURPOSE:

To describe the Food and Drug Administration (FDA) review and approval of sunitinib malate (Sutent). Sunitinib received regular approval for the treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Additionally, sunitinib received accelerated approval for the treatment of advanced renal cell carcinoma.

EXPERIMENTAL DESIGN:

For the GIST indication, FDA reviewed data from a randomized, placebo-controlled trial with supportive evidence from a single-arm study. For the advanced renal cell carcinoma indication, FDA reviewed data from two single-arm studies of patients with cytokine-refractory metastatic renal cell carcinoma.

RESULTS:

In patients with imatinib refractory or intolerant GIST, time-to-tumor progression of sunitinib-treated patients was superior to that of placebo-treated patients. Median time-to-tumor progression of sunitinib-treated patients was 27.3 weeks, compared with 6.4 weeks for placebo-treated patients (P < 0.0001). Partial responses were observed in 6.8% of sunitinib-treated patients. In patients with metastatic renal cell carcinoma, partial responses were observed in 25.5% (95% confidence interval, 17.5, 34.9) and 36.5% (95% confidence interval, 24.7, 49.6) of patients treated with sunitinib. Median response durations were 27.1 and 54 weeks. The most common adverse events attributed to sunitinib included diarrhea, mucositis, skin abnormalities, and altered taste. Reductions in left ventricular ejection fraction and severe hypertension were also more common in sunitinib-treated patients.

CONCLUSIONS:

On January 26, 2006, the FDA approved sunitinib for the treatment of patients with imatinib refractory or intolerant GIST. Accelerated approval was granted for the treatment of advanced renal cell carcinoma.

• Authors: Vicki L Goodman, Edwin P Rock, Ramzi Dagher, Roshni P Ramchandani, Sophia Abraham, Jogarao V S Gobburu, Brian P Booth, S Leigh Verbois, David E Morse, Cheng Yi Liang, Nallaperumal Chidambaram, Janet X Jiang, Shenghui Tang, Kooros Mahjoob, Robert Justice, Richard Pazdur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 5 Pg. 1367-73 (Mar 01 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17332278 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Benzamides
• Indoles
• Piperazines
• Pyrimidines
• Pyrroles
• Imatinib Mesylate
• Sunitinib

Topics

• Antineoplastic Agents (therapeutic use)
• Benzamides
• Carcinoma, Renal Cell (drug therapy)
• Drug Approval
• Drug Resistance, Neoplasm
• Gastrointestinal Stromal Tumors (drug therapy)
• Humans
• Imatinib Mesylate
• Indoles (therapeutic use)
• Kidney Neoplasms (drug therapy)
• Piperazines (therapeutic use)
• Pyrimidines (therapeutic use)
• Pyrroles (therapeutic use)
• Randomized Controlled Trials as Topic
• Sunitinib
• United States
• United States Food and Drug Administration