In selected patients with unresectable colorectal liver metastases, liver transplantation plus chemotherapy significantly boosted overall survival as compared with chemotherapy alone in the multicenter, European TRANSMET trial, presented at the 2024 ASCO Annual Meeting.¹ The combined approach led to a 5-year overall survival rate of 73% compared with 9% for patients treated with chemotherapy alone.

“Liver transplantation plus chemotherapy offers a potential cure to patients with cancer with otherwise poor long-term outcomes…. These data suggest that patients with colorectal liver metastases [who have undergone transplant] have similar survival as those [who undergo transplant] for established liver transplantation indications … and support liver transplantation as a new standard option that could change our practice,” said Rene Adam, MD, PhD, of the Department of Hepato-Biliary Surgery, Cancer, and Transplantation at Paul Brousse Hospital, Villejuif, France.

TRANSMET is the first randomized trial evaluating the efficacy of liver transplantation plus chemotherapy in this patient population. Among the reasons for its success, he said, were the “very, very strict” criteria for patient selection. Candidates were identified by the center’s tumor board and validated by consensus of an independent multidisciplinary expert committee that included four expert surgeons to determine unresectability, as well as two medical oncologists and one radiologist. The results basically refute the long-standing perception that there is no role for local treatment in advanced metastatic disease,” he indicated.

These results support liver transplantation as a new standard option [in patients with unresectable colorectal liver metastases] that could change practice.

— Rene Adam, MD, PhD

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About TRANSMET

Eligibility was restricted to patients with colorectal cancer who were aged 65 or younger and had undergone gold-standard resection of the primary tumor and had surgery-confirmed unresectable liver metastases. Patients had a good performance status, no extrahepatic disease, a partial response or stable disease after chemotherapy, no BRAF mutation, low carcinoembryonic antigen levels, and adequate platelet and white blood cell counts.

Of 157 cases submitted to the independent committee, from patients at 20 centers in France, Belgium, and Italy, 94 patients were selected for the study. Patients were randomly assigned to continue chemotherapy or be placed on a transplant waiting list, prioritized so the transplant could be performed within 2 months after the last chemotherapy treatment. Overall survival at 5 years was the primary endpoint.

The median number of nodules was 20, the median maximum diameter was 55 mm in the transplant arm and 50 mm in the control arm, and the total number of chemotherapy cycles was 21 and 17, respectively. The most common chemotherapy in both arms was irinotecan-based.

Outcomes After Transplant

The intent-to-treat population included 47 patients in each arm, whereas the per-protocol analysis included 36 in the transplant arm and 38 in the nontransplant arm. Nine patients in the intent-to-treat transplant group had disease progression and did not receive a liver transplant; two patients were excluded from the per-protocol analysis, including one whose transplant was performed more than 3 months after the last chemotherapy cycle. In the control arm, nine patients did not receive the assigned treatment; two patients were transplanted out of the protocol, and seven underwent liver resection. After transplant, about two-thirds of patients received chemotherapy.

At a median follow-up of 59 months, the intent-to-treat analysis showed a 5-year overall survival rate for the transplant/chemotherapy arm of 57%, vs 13% of patients treated with chemotherapy alone (hazard ratio [HR] = 0.37; P = .0003). Results were even more favorable for transplantation in the per-protocol analysis of 74 patients, where the 5-year overall survival rate was 73% in the transplant/chemotherapy group and 9% in the chemotherapy-alone group (HR = 0.16; P < .0001); progression-free survival rates, respectively, were 33% vs 4% at 3 years and 20% vs 0% at 5 years (HR = 0.34; P < .0001).

Recurrence Rates

Among the 36 patients who received a transplant, 26 (72%) had disease recurrence: 14 in the lungs, 3 in the lymph nodes, 1 in the liver, and 8 at other sites or multiple sites. Among those with disease recurrence after receiving a transplant, 12 (46%) underwent rescue surgery or ablation.

Altogether, 15 of the 36 patients (42%) in the transplant per-protocol group had no evidence of disease after 50 months of follow-up. In contrast, in the chemotherapy per-protocol group, all but one patient (97%) had disease progression. After switching to a new chemotherapy regimen, one patient had no evidence of disease (3%).

“These results support liver transplantation as a new standard option that could change practice,” Dr. Adam added. 

Expert Point of View

ASCO discussant Major Kenneth Lee, MD, PhD, Associate Professor of Surgery, Penn Medicine, Philadelphia, said TRANSMET shows that liver transplant in patients with unresectable colorectal liver metastases can indeed extend overall survival. The foundation for TRANSMET comprises the historically poor outcomes for unresectable liver metastases, with estimated 5-year survival times of around 10%. Studies of liver transplant for this indication from several decades ago were not encouraging but did help identify factors for long-term survival. Additionally, he said, “we got better at treating liver metastases and in doing transplant,” so subsequent trials did show value for transplant. The SECA-II trial, for one, found an 83% survival at 5 years after liver transplant2 and paved the way for the TRANSMET study.

Patient selection was appropriate, he said—“not so liberal you worry about futile transplant but not so stringent you can’t enroll patients.” With the per-protocol analysis showing a 73% overall survival rate at 5 years, vs 9% with chemotherapy alone, “it’s safe to say this works,” Dr. Lee concluded.

Nevertheless, it is not simple to identify the right patients for transplant. In TRANSMET, 40% of patients deemed eligible did not ultimately receive a liver. “These centers were very sophisticated in submitting patients. It shows how difficult it is to select the right patients and actually get them to transplant,” he said. This reality is mirrored by findings from a living donor transplant program in Toronto, where of 81 patients referred, only 7 completed transplant; their 3-year overall survival was 100%.³

Dr. Lee concluded that “there is much to unpack” and questions to answer about liver transplantation as an approach to treating liver metastases. “I’m not sure it is even possible to develop standard algorithms to get patients to transplant when we have such a heterogeneous population,” he added.

DISCLOSURE: Dr. Adam reported no conflicts of interest. Dr. Lee reported no conflicts of interest.

REFERENCES

1. Adam R, Piedvache C, Chiche L, et al: Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET). 2024 ASCO Annual Meeting. Abstract 3500. Presented June 2, 2024.

2. Dueland S, Syversveen T, Solheim JM, et al: Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases. Ann Surg 271:212-218, 2020.

3. Rajendran L, Claasen MP, McGilvray ID, et al: Toronto management of initially unresectable liver metastasis from colorectal cancer in a living donor liver transplant program. J Am Coll Surg 237:231-242, 2023.