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

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.