Although liver resection is the best treatment for colorectal liver metastases (CLM), only 20% of cases are initially resectable, while others require conversion chemotherapy (CTx) before undergoing secondary resection after downsizing.¹ Some patients, however, have definitively unresectable CLM for which CTx is the standard of care but is unable to achieve long-term survival.¹ Liver transplantation (LT) is a potential alternative treatment option for these patients but was contraindicated in the 2000s due to low 5-year survival rates.¹ More recently, improved outcomes for LT have been reported with better patient selection and increased efficacy of CTx.¹ However, strong evidence for clinical benefit is still needed due to the scarcity of organs and the perception that local treatment does not have a role in advanced metastatic disease.¹ As such, the TransMet trial was conducted to assess the efficacy of LT + CTx compared to CTx only for patients with unresectable CLM.¹ The results of the study were recently presented at the 2024 ASCO Annual Meeting by Dr. René Adam from the Paul Brousse Hospital, France.¹

In this randomized study, patients ≤65 years with non-BRAF mutated colorectal cancer and confirmed unresectability of CLM by expert surgeons were recruited.¹ These patients also had no extrahepatic disease, partial response or stability with CTx (≥3 months, ≤3 lines), gold standard resection of the primary tumor, platelet count >80,000/mL and blood cell count >2,500/mL, and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1).¹ In total, 94 patients were randomized 1:1 to received LT + CTx (n=47) or CTx only (n=47).¹ However, 9 patients in the LT + CTx group did not receive LT due to progression during the waiting time, while 1 patient received LT on progression and another >3 months from CTx (n=36 included in per protocol).¹ In the CTx-only group, 2 patients received LT out of protocol while 7 received a liver resection (n=38 included in per protocol).¹ The primary endpoint of the study was overall survival (OS) at 5 years while the secondary endpoints were OS at 3 years, progression-free survival (PFS) at 3 and 5 years, and recurrence rates at 3 and 5 years.¹

In the intent-to-treat analysis, 5-year OS was 57% in the LT + CTx group compared to 13% in the CTx-only group (hazard ratio [HR]=0.37; 95% CI: 0.21-0.65; p=0.0003) with a median follow-up of 59 months.1 In the per-protocol analysis, 5-year OS was 73% in the LT + CTx group compared to 9% in the CTx-only group (HR=0.34; 95% CI: 0.20-0.57; p<0.0001).¹ For the secondary endpoints, the 3-year PFS was 33% in the LT + CTx group and 4% in the CTx-only group, while the 5-year PFS was 20% in the LT + CTx group and 0% in the CTx-alone group (HR=0.34; p<0.0001; 95% CI: 0.20-0.57).¹ In the per-protocol population, 26 out of 36 patients in the LT + CTx group experienced recurrence (72%), of which more than half occurred in the lungs (n=14).¹ However, this recurrence were rescued by surgery or ablation in 12 patients (46%), leading to 15 patients in the LT + CTx group (42%) with no evidence of disease (NED).¹ In the CTx-only group, 37 out of 38 patients developed disease progression (97%), and after undergoing a new CTx regimen, only 1 patient showed NED (3%).¹

In summary, LT + CTx significantly improved OS and PFS in selected patients with unresectable CLM compared to CTx alone.¹ Through rigorous patient selection and prioritization for organ allocation, this study also found that transplanted patients for CLM have similar survival rates as those transplanted for other established LT indications.¹ These results thus support LT + CTx as a new standard treatment option for cancer patients with otherwise poor long-term outcomes.¹