Rechallenge with mTOR inhibitors in metastatic renal cell carcinoma patients who progressed on previous mTOR inhibitor therapy

Oncology. 2013;85(1):8-13. doi: 10.1159/000350005. Epub 2013 Jun 21.

Abstract

Objective: To determine if mammalian target of rapamycin (mTOR) inhibitor (everolimus or temsirolimus) rechallenge in the third- or fourth-line setting after sequential use of a vascular endothelial growth factor receptor (VEGF)-targeted agent and an mTOR inhibitor is a feasible and effective treatment strategy in patients with metastatic renal cell carcinoma (mRCC).

Methods: Patients who received a VEGF-targeted agent, an mTOR inhibitor and rechallenge with a second mTOR inhibitor at 2 institutions (Hôpital Européen Georges-Pompidou and Vienna Medical School) between 30 March 2001 and 15 September 2011 were included. Analyses of radiographic images were performed according to the Response Evaluation Criteria in Solid Tumors, version 1.0, to determine the objective response rate and treatment duration (TD).

Results: Twelve patients met the inclusion criteria. Following 1 or 2 VEGF receptor-tyrosine kinase inhibitors, 7 patients firstly received everolimus and 5 patients received temsirolimus. Irrespective of treatment sequence, 6 of 12 patients (50%) responded to everolimus and 4 of 12 patients (33%) responded to temsirolimus; 3 patients (25%) did not respond to either. Median TDs (95% confidence interval) for everolimus → temsirolimus and temsirolimus → everolimus sequences were 10.3 months (8.8-19.2 months) and 5.8 months (2.9-19.3 months), respectively.

Conclusions: Despite the limited number of patients, this highlights the feasibility of utilizing mTOR rechallenge as an integral part of sequential treatment strategies in mRCC.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Everolimus
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Retrospective Studies
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • temsirolimus
  • Everolimus
  • MTOR protein, human
  • Receptors, Vascular Endothelial Growth Factor
  • TOR Serine-Threonine Kinases
  • Sirolimus