Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network

Ann Oncol. 2010 Sep;21(9):1834-1838. doi: 10.1093/annonc/mdq029. Epub 2010 Feb 12.

Abstract

Background: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients.

Patients and methods: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed.

Results: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up.

Conclusion: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Benzenesulfonates / therapeutic use
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / secondary
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 11 / genetics*
  • Chromosomes, Human, X / genetics*
  • Everolimus
  • Female
  • Gene Fusion*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Indoles / therapeutic use
  • Interferon-alpha / therapeutic use
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / therapeutic use
  • Pyrroles / therapeutic use
  • Research Report
  • Retrospective Studies
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Sorafenib
  • Sunitinib
  • Survival Rate
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Translocation, Genetic / genetics*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Young Adult

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Benzenesulfonates
  • Immunosuppressive Agents
  • Indoles
  • Interferon-alpha
  • Phenylurea Compounds
  • Pyridines
  • Pyrroles
  • TFE3 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Everolimus
  • Sorafenib
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sunitinib
  • Sirolimus