Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies

Br J Cancer. 2011 Nov 22;105(11):1635-9. doi: 10.1038/bjc.2011.389. Epub 2011 Oct 27.

Abstract

Background: Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus.

Patients and methods: Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (n=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan-Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS.

Results: Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4-22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (P=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses.

Conclusions: Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzenesulfonates / therapeutic use*
  • Bevacizumab
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Everolimus
  • Female
  • Humans
  • Interferons / administration & dosage
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / therapeutic use*
  • Retrospective Studies
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • Sorafenib
  • Treatment Failure
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal, Humanized
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Bevacizumab
  • Interferons
  • Everolimus
  • Sorafenib
  • Sirolimus