In the European TransMet trial, reported in The Lancet, Adam et al found that liver transplantation plus chemotherapy improved overall survival vs chemotherapy alone in patients with permanently unresectable colorectal cancer liver metastases.
Study Details
In the open-label trial, 94 patients (intention-to-treat [ITT] population) aged 18 to 65 years with liver metastases from resected BRAF-nonmutated colorectal cancer responsive to systemic chemotherapy and no extrahepatic disease were enrolled at 20 European tertiary centers between February 2016 and July 2021. Patients were randomly assigned to receive liver transplantation plus chemotherapy (n = 37) or chemotherapy alone (n = 37). The median number of metastases at diagnosis was 20 in both groups.
Liver transplantation was performed within 2 months of the last chemotherapy cycle. At random assignment, the transplantation/chemotherapy group had received a median of 21.0 chemotherapy cycles and the chemotherapy-alone group had received 17.0 cycles in up to three lines of chemotherapy. In first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) had received triplet regimens; 76 (80%) received targeted therapy. Patients undergoing transplantation received tailored immunosuppressive treatment and postoperative chemotherapy; the chemotherapy group received continued chemotherapy. The primary endpoints were 5-year overall survival in the ITT and per-protocol populations.
Key Findings
Among the ITT population, a total of 11 patients in the transplantation/chemotherapy group and 9 in the chemotherapy-alone group did not receive assigned treatment. The per-protocol population thus consisted of 36 patients in the transplantation/chemotherapy group and 38 in the chemotherapy-alone group.
Median follow-up was 59.3 months (interquartile range = 42∙4–60.2 months). In the ITT population, 5-year overall survival was 56.6% (95% confidence interval [CI] = 43.2%–74.1%) in the transplantation/chemotherapy group vs 12.6% (95% CI = 5.2%-30.1%) in the chemotherapy-alone group (hazard ratio [HR] = 0.37, 95% CI = 0.21–0.65, P = .0003). Median overall survival was not reached vs 29.7 months.
In the per-protocol population, 5-year overall survival was 73.3% (95% CI = 59.6%–90.0%) in the transplantation/chemotherapy group vs 9.3% (95% CI = 3.2%–26.8%) in the chemotherapy group. Median overall survival was not reached vs 26.6 months (HR = 0.16, 95% CI = 0.07–0.33, P < .0001).
The investigators concluded: “In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases.”
René Adam, PhD, of the Department of Hepatobiliary Surgery and Transplantation, AP-HP Hôpital Paul Brousse, University of Paris-Saclay, Villejuif, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the French National Cancer Institute and Assistance Publique–Hôpitaux de Paris. For full disclosures of all study authors, visit TheLancet.com.
