FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma

Oncologist. 2010;15(4):428-35. doi: 10.1634/theoncologist.2009-0178. Epub 2010 Mar 23.

Abstract

This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-alpha versus those receiving temsirolimus alone or in combination with IFN-alpha. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-alpha arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-alpha did not lead to a significant difference in OS compared with IFN-alpha alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-alpha arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Drug Approval*
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Intracellular Signaling Peptides and Proteins / drug effects
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Protein Serine-Threonine Kinases / drug effects
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survival Analysis
  • TOR Serine-Threonine Kinases
  • United States
  • United States Food and Drug Administration
  • Young Adult

Substances

  • Antineoplastic Agents
  • Immunologic Factors
  • Interferon-alpha
  • Intracellular Signaling Peptides and Proteins
  • temsirolimus
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases
  • Sirolimus