Liver Transplantation plus Chemotherapy vs. Chemotherapy Alone in Metastatic Colorectal Cancer

Patients with metastatic colorectal cancer with liver-only metastases benefit from regional therapies, including surgery. The selective application of liver transplantation in these patients is still debated. Now, investigators report results of the TransMet trial, which involved patients with unresectable liver-confined, BRAF wild-type metastatic colorectal cancer who had achieved stable disease or response to ≥3 months of chemotherapy. Patients were randomized to continue chemotherapy or to undergo liver transplantation followed by additional chemotherapy.

Of the 94 patients enrolled, 15% had right-sided primaries, 32% had RAS mutations, nearly 100% presented with synchronous metastases, and 87% achieved either response or stable disease to first-line chemotherapy. The average number of liver metastases was 20, and the average number of treatment cycles at randomization was 21 in the transplant arm and 17 in the chemotherapy arm. Of the 47 transplant-arm patients, 38 (81%) underwent transplantation, and of the 47 chemotherapy-alone patients, 9 (19%) underwent surgical intervention (hepatic resection in 7, and liver transplantations in 2).

The primary endpoint, 5-year overall survival, was superior for transplant versus chemotherapy in the intention-to-treat (56.6% vs. 12.6%) and per-protocol analyses (73.2% vs. 9.3%). Three-year overall survival was 65.5% and 38.9%. Of the transplant-arm patients who underwent transplantation, 72% experienced metastatic recurrence, largely in the lungs and lymph nodes, and 46% underwent surgery or local ablation, with a secondary progression-free survival rate of 36.1% at 5 years. Transplantation appeared tolerable, with comparable rates of serious adverse events for the transplant and chemotherapy arms (80% and 83%).