The risk of cancer in kidney transplant recipients may be reduced in those maintained on everolimus and reduced cyclosporine

Kidney Int. 2017 Apr;91(4):954-963. doi: 10.1016/j.kint.2016.11.008. Epub 2017 Jan 18.

Abstract

Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine. Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the seven-year risk of incident cancer and other graft outcomes among a subgroup of recipients who had participated in the A2309 study using adjusted Cox proportional hazard models. Of 95 recipients, 66 were randomized to everolimus (1.5 mg or 3 mg) with reduced cyclosporine and 29 received mycophenolate sodium and standard exposure cyclosporine. Compared to mycophenolate sodium and standard exposure cyclosporine, everolimus treatment was associated with unadjusted hazard ratios of 0.28 (95% confidence interval 0.11-0.74), 0.39 (0.16-0.98) and 0.41 (0.23-0.71), respectively for nonmelanoma skin cancer, non-skin cancers and any cancers. Interestingly, the adjusted hazard ratios were 0.34 (0.13-0.91), 0.35 (0.09-1.25) and 0.32 (0.15-0.71), respectively. There was no association between treatment groups and rejection, graft loss or death. Compared to standard-exposure cyclosporine, everolimus with reduced exposure to cyclosporine may be associated with a reduced risk of cancer, particularly for non-melanoma skin cancer. Thus, if confirmed in larger patient cohorts, de novo use of everolimus with reduced exposure to calcineurin inhibitors may enable a reduction in cancer burden after transplantation.

Keywords: A2309 trial; ANZDATA; cancer; cyclosporine; epidemiology; everolimus.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia / epidemiology
  • Calcineurin Inhibitors / administration & dosage*
  • Calcineurin Inhibitors / adverse effects
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Drug Therapy, Combination
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Incidence
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology
  • Neoplasms / prevention & control*
  • New Zealand / epidemiology
  • Proportional Hazards Models
  • Protective Factors
  • Registries
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Mycophenolic Acid