CONFERENCE UPDATE: ASCO 2024
Liver transplantation + chemotherapy improves survival rates for patients with unresectable colorectal liver metastases
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