title: Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Division of Drug Oncology Products, U.S. Food and Drug Administration, Sliver Spring, Maryland 20903, USA. vicki.goodman@fda.hhs.gov
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Goodman
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Rock
authors.forename: Ramzi
authors.initials: R
authors.lastname: Dagher
authors.forename: Roshni P
authors.initials: RP
authors.lastname: Ramchandani
authors.forename: Sophia
authors.initials: S
authors.lastname: Abraham
authors.forename: Jogarao V S
authors.initials: JV
authors.lastname: Gobburu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Booth
authors.forename: S Leigh
authors.initials: SL
authors.lastname: Verbois
authors.forename: David E
authors.initials: DE
authors.lastname: Morse
authors.forename: Cheng Yi
authors.initials: CY
authors.lastname: Liang
authors.forename: Nallaperumal
authors.initials: N
authors.lastname: Chidambaram
authors.forename: Janet X
authors.initials: JX
authors.lastname: Jiang
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.forename: Kooros
authors.initials: K
authors.lastname: Mahjoob
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077210:Sunitinib; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib