De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients: A trial-based linkage study

Tracey Ying, Germaine Wong, Wai Lim, John Kanellis, Helen Pilmore, Scott Campbell, Rosemary Masterson, Rowan Walker, Philip O'Connell, Graeme Russ, Steven Chadban

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Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks. Two hundred seventy-nine patients (192 everolimus, 87 control) were followed for a median of 9 years (IQR 6.7, 11.2). Compared with control, everolimus use was not associated with a reduction in the risk of incident cancer, NMSC, or cancer-related death (unadjusted HR [95% CI] 0.86 [0.49-1.48], 0.58 [0.30-1.12], and 1.18 [0.32-4.38], respectively). Subgroup analyses showed a 56% reduction for NMSC in patients randomized to everolimus + reduced-dose calcineurin-inhibitor versus control (unadjusted HR 0.44 [0.21-0.92]), which remained significant after adjusting for age, gender and smoking (adjusted HR 0.45 [0.21-0.96]). Although de novo or early switch to everolimus did not alter the 9-year risk of incident cancer or cancer-related death, everolimus with reduced-dose calcineurin-inhibitor strategy may reduce the long-term risk of NMSC.

Original languageEnglish
Pages (from-to)2977-2986
Number of pages10
JournalAmerican Journal of Transplantation
Issue number12
Publication statusPublished - 1 Dec 2018


  • cancer/malignancy/neoplasia: registry/incidence
  • clinical research/practice
  • immunosuppressant - calcineurin inhibitor (CNI)
  • immunosuppressant - mechanistic target of rapamycin: everolimus
  • kidney transplantation/nephrology

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