Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis

J Cancer Res Clin Oncol. 2014 May;140(5):823-7. doi: 10.1007/s00432-014-1610-x. Epub 2014 Feb 21.


Purpose: Renal cell carcinoma (RCC) is the most common renal tumor and accounts for nearly 3 % of adult cancers. In the recent years, seven new targeted agents have been approved changing the treatment in metastatic RCC dramatically. So far, however, it remains unclear which sequence is best for those patients. This study analyzed retrospectively the outcome of patients treated with everolimus after failure of a vascular endothelial growth factor receptor-directed therapy and which therapies were used after everolimus.

Patients and methods: In a retrospective analysis, patients receiving everolimus after failure of first-line VEGFR-directed therapy have been analyzed in regard to response, duration of treatment and subsequent therapies. In total, the data of 81 patients have been analyzed.

Results: The most observed first-line therapy was sunitinib followed by sorafenib. Thirty-two patients received everolimus as second-line therapy, and 49 as third-line therapy. The median duration of treatment with everolimus was 4.5 months. Seventy-seven of eighty-one patients (95 %) received a further therapy after discontinuation of everolimus. The agents administered beyond were sunitinib (28.6 %), sorafenib (28.6 %) and 42.8 % received other therapies. Twenty-seven patients received an additional sequence of therapy (fourth to fifth line). Fifty-eight percentage of patients have still been alive at time of analysis.

Conclusion: The duration of everolimus therapy beyond failure of anti-VEGF-directed therapy and the reported time to progression was in the range of the RECORD-1 trial in daily practice as well. After failure of everolimus, reexposure to tyrosine kinase inhibitors is a common clinical practice and demonstrates a clinical benefit of therapies beyond everolimus.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Clinical Trials as Topic
  • Everolimus
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Pyrroles / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Retrospective Studies
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Sorafenib
  • Sunitinib
  • TOR Serine-Threonine Kinases / antagonists & inhibitors


  • Indoles
  • Phenylurea Compounds
  • Pyrroles
  • Niacinamide
  • Everolimus
  • Sorafenib
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib
  • Sirolimus