Transplant Trial Watch

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

Schnitzbauer, A. A., et al.

Annals of Surgery 2020 [record in progress].

This is an exploratory analysis of the SiLVER-trial that aimed to investigate the survival benefit of sirolimus in patients receiving liver transplantation for hepatocellular carcinoma (HCC).

Participants in the SiLVER-trial were randomized to either the sirolimus-based inmunosuppression group or the mammalian target of rapamycin (mTOR) inhibitor-free immunosuppression group.

525 patients undergoing liver transplantation for HCC were included in the original trial, of which 508 were included in the intention-to-treat (ITT) analysis. All patients from the ITT analysis were included in this study.

The primary outcome was overall survival. The secondary outcomes were disease-free survival and HCC recurrence.

72.4 months (95% CI 70.7–74.1) (median)

CET Conclusions
This is a very interesting, large, multinational RCT in liver transplantation for HCC, comparing one immunosuppression regimen including sirolimus with a regimen excluding it. The study was large (525 randomized patients) and conducted with an intention to treat analysis. The original study was powered for disease-free survival at 5 years after transplantation and did no show a statistically significant difference between the two study arms for this outcome, although overall survival was better in the sirolimus arm. This analysis, which centers on establishing a minimum duration of 3 months treatment with sirolimus, the potential anti-cancer effect of sirolimus is seen; sirolimus treatment for greater than 3 months was associated with improved overall survival. At 2 years of follow-up, 78% of patients in the sirolimus arm were still receiving this medication. In the subgroup of patients with AFP greater than, or equal to, 10ng/mL, sirolimus treatment for over 3 months had an even greater impact on overall survival. This was an exploratory analysis of data but made use of thorough analysis and appropriate multivariate statistical analysis.

Trial registration - NCT00355862; EudraCTnumber - 2005-005362-36

Funding source
Industry funded