Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.
Geissler EK, Schnitzbauer AA, et al.Transplantation 2016 Jan;100(1):116-25
Aims
To investigate whether sirolimus based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC)
Interventions
Patients were randomized into two groups and received either center-specific mTOR inhibitor-free, generally calcineurin inhibitor-based, immunosuppressive protocol (control group), or mTOR inhibitor-free immunosuppression for 4-6 weeks, incorporated with sirolimus (4-10ng/mL) either as monotherapy or as a combination therapy with non-mTOR inhibitor-based drugs (study group).
Participants
525 LTx recipients aged ≥18 years with HCC
Outcomes
The primary outcome measured was recurrence-free survival (RFS). Secondary outcomes were overall survival (OS) and RFS/OS in the high-risk and low-risk subgroups.
Follow-up
5-8 years
CET Conclusions
This is a large and important study investigating the use of m-Tor inhibitors after liver transplantation in patients with hepatocellular carcinoma. Two hundred and sixty-four patients received the standard immunosuppression of the unit involved without an m-Tor inhibitor, while 261 patients received immunosuppression containing an m-Tor inhibitor (Sirolimus). Randomisation to Sirolimus or not took place four to six weeks after transplantation. There is a very detailed analysis presented of risk factors and outcomes in patients with hepatocellular carcinoma within and out with the Milan criteria. Basically, it appears that Sirolimus in liver transplant recipients with HCC does not improve long-term recurrence-free survival in these patients, but there is a benefit evident in the first three to five years especially in low risk patients. This very impressive multicentre international trial (SiLVER trial) does provide evidence for selective immunosuppression in liver transplant recipients with hepatocellular carcinoma.
Data analysis
Modified intention-to-treat analysis
Trial registration
EudraCT - 2005-005362-36; Clinicaltrials.gov - NCT00355862