Transplant Trial Watch

Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.

Mazzaferro, V., et al.

Lancet Oncology 2020; 21(7): 947-956

The aim of this study was to examine the efficacy of liver transplantation following successful downstaging of hepatocellcular carcinoma (HCC).

Patients were randomized to either the liver transplantation (intervention) group or the non-transplantation (control) group.

45 patients with HCC beyond the Milan criteria.

In phase 2b of the study, the primary endpoint was 5-year tumor event-free survival, whereas in phase 3, the primary outcome was 5-year overall survival.

Median 71 months (IQR 60–85)

CET Conclusions
This interesting pragmatic multicenter trial randomized patients with HCC outside of the Milan criteria to downstaging therapy followed by transplantation or non-transplantation therapy if downstaging was successful. The study demonstrated a significant tumor-free and overall survival benefit to transplantation, with overall survival at 5-years of 77.5% vs. 31.2%. The study is well-designed and thought out, but unfortunately the study stopped recruitment early (after 45 randomizations of the proposed 260) due to changes in the donation and allocation system in Italy. This may impact the results, as the demographics perhaps suggest a higher-risk profile in the control group (more hepatitis C, more recurrent HCC). It is worth noting that randomization only occurred after downstaging, so patients lost prior to this were excluded from the intent-to-treat analysis.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Trial registration - NCT01387503

Funding source
Non-industry funded