Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: results of a pooled analysis of non-interventional studies

Eur J Cancer. 2015 Nov;51(16):2368-74. doi: 10.1016/j.ejca.2015.07.030. Epub 2015 Aug 11.


Aim: To assess the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who failed one or two anti-VEGF therapies.

Patients and methods: Data from four prospective, non-interventional studies conducted in Germany, France, Greece and Austria were pooled for this analysis. Patients with mRCC of any histology (clear cell or non-clear cell) were included. VEGF-refractory patients received everolimus 10mg/day until disease progression or unacceptable toxicity. The primary objective was to determine everolimus efficacy as measured by time to progression (TTP; from baseline to progression).

Results: The overall population comprised 632 patients; 493 patients received everolimus in the second-line setting. Most patients were of favourable/intermediate MSKCC risk (91%), had clear cell mRCC (89%), and had undergone nephrectomy (89%). Median TTP was 6.3months (95% confidence interval [CI], 5.9-6.8) for the overall population and 6.4months (95% CI, 5.8-6.9) for the second-line everolimus population. Similarly, median progression-free survival was 5.5months (95% CI, 5.0-6.1) for the overall population and 5.8months (95% CI, 5.0-6.4) for second-line everolimus population. Best tumour response (n=349) was complete or partial remission in 12% of patients and stable disease in 59% of patients. Overall population median overall survival (OS) was 11.2months (95% CI, 9.0-not reached). Commonly reported adverse events (AEs) (any grade) were stomatitis (25%), anaemia (15%) and asthenia (11%).

Conclusions: Results of this pooled analysis provide evidence of safety and effectiveness of second-line everolimus in routine clinical use and support everolimus as a standard of care for VEGF-refractory patients with mRCC.

Keywords: Everolimus; Metastatic renal cell carcinoma; Non-interventional; Sequential targeted therapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / secondary
  • Chemotherapy, Adjuvant
  • Disease Progression
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • Europe
  • Everolimus / adverse effects
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Nephrectomy
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Everolimus