Chemo plus liver transplant prolongs survival in unresectable colorectal liver metastases

Liver transplantation (LT) in combination with chemotherapy, as opposed to chemotherapy alone, can provide a meaningful improvement in survival among patients with unresectable colorectal liver metastases, suggest the results of the TRANSMET trial presented at ESMO GI 2024.

In addition, post-LT chemotherapy has an acceptable toxicity and is feasible in this population. Patients who received LT plus chemotherapy also show no major long-term deterioration in quality of life (QOL).

“LT plus chemotherapy significantly improves overall survival (OS) and progression-free survival (PFS) in selected patients with unresectable colorectal liver metastases compared to chemotherapy alone, through a rigorous patient selection and a prioritization for organ allocation,” said lead author Dr Maximiliano Gelli from Hôpital Paul Brousse AP-HP in Villejuif, France.

TRANSMET submitted patients with definitively unresectable colorectal liver metastases from resected BRAF nonmutated colorectal cancer, responding to chemotherapy (≥3 months, ≤3 lines) and with no extrahepatic disease, to an independent experts committee. Subsequently, Gelli and his team randomized eligible patients in a 1:1 ratio to receive LT plus chemotherapy or chemotherapy alone.

OS at year 5 was the primary endpoint, while secondary endpoints included PFS and QOL. TRANSMET was designed to distinguish a difference of 40 percent in OS, from 10 percent with chemotherapy alone to 50 percent with LT plus chemotherapy (2-sided α level 5- to 90-percent power).

Improved survival

Overall, the experts committee assessed 157 patients from 20 centres across three countries from February 2016 to July 2021. Of these, 94 (60 percent) were randomized to receive either LT plus chemotherapy (n=47) or chemotherapy alone (n=47). The median number and maximal diameter of the metastases at diagnosis were 20 and 51.5 mm, respectively. [ESMO GI 2024, abstract 1O]

Patients achieved objective response after a median number of 20 chemotherapy cycles during 1 (44 percent), 2 (40 percent), or 3 (16 percent) lines. Nine patients (19 percent) in each group, however, did not receive the allocated treatment due to oncological reasons (LT plus chemotherapy arm) or unexpected curative procedures (chemotherapy alone arm).

The intention-to-treat analysis revealed a significantly greater 5-year OS with the combination treatment compared with chemotherapy alone (57 percent vs 13 percent; hazard ratio [HR], 0.37, 95 percent confidence interval [CI], 0.21‒0.65; p=0.0003).

In per protocol analysis, the rate of 5-year OS was significantly greater with LT plus chemotherapy than with chemotherapy alone (73 percent vs 9 percent; HR, 0.16, 95 percent CI, 0.07‒0.33; p<0.0001).

A similar trend was observed for PFS, with a median of 17.4 months with the combination treatment and 6.4 months with chemotherapy alone (HR, 0.34, 95 percent CI, 0.20‒0.58).

Among patients who receive LT, 28 (74 percent) experienced a recurrence, which was treated either by surgery (36 percent) or local ablation (11 percent), and 15 (40 percent) were considered disease-free.

Assessment of QOL showed a trend towards a decline in physical functioning and main symptoms among those who received chemotherapy alone.

“These results support LT as a new standard option for selected patients with liver-only, definitively unresectable colorectal liver metastases,” Gelli said.