Transplantation for unresectable colorectal liver metastases?

For carefully selected patients with unresectable colorectal liver metastases, the combination of liver transplantation and chemotherapy significantly improves overall survival compared with chemotherapy alone, according to results from the TRANSMET trial.

The combination treatment resulted in a 73% five-year survival rate, compared with 9% for patients who received chemotherapy alone.

“Liver transplantation combined with chemotherapy offers a potential treatment for cancer patients with poor long-term outcomes,” lead researcher René Adam, MD, PhD, said while presenting the latest findings at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting.

But one of the ASCO discussants, Major K. Lee, MD, associate professor of surgery at the University of Pennsylvania School of Medicine in Philadelphia, cautioned that careful patient selection will be important.

Chemotherapy remains the standard of care for patients with completely unresectable colorectal liver metastases, but historically these patients have had poor long-term outcomes.

Adam said liver transplants have shown promise in this patient population, but “strong evidence” of clinical benefit is needed, given the shortage of organs and the recognition that “local treatments are useless in advanced metastatic disease.”

TRANSMET is the first randomized trial to evaluate the effectiveness of combining liver transplantation with chemotherapy in this patient population, and the eligibility criteria were “very strict,” Adam explained.

Eligibility was limited to patients aged 65 years or younger with good performance status (ECOG 0 or 1). Patients had surgeon-confirmed unresectable colorectal liver metastases and had undergone gold standard resection of the primary tumor. Patients also had no extrahepatic disease, had a partial or stable response to chemotherapy, and BRAF mutations, low carcinoembryonic antigen levels, and adequate platelet and white blood cell counts.

A total of 94 patients were randomized to continue chemotherapy or to receive liver transplant and chemotherapy. Patients on the transplant waiting list were prioritized for timely access to an organ and could undergo liver transplant within 2 months of their last chemotherapy treatment.

In an intention-to-treat analysis of all patients (n=47 per group), the 5-year survival rate was 57% in the transplant plus chemotherapy group compared with 13% in the chemotherapy alone group (hazard ratio[HR]0.011-0.05). [HR]0.37; P = .0003).

However, nine patients in the intention-to-treat transplant group did not undergo liver transplantation because of disease progression, and two others were excluded from the per-protocol analysis, including one patient who underwent liver transplantation more than 3 months after the last chemotherapy treatment.

The per-protocol analysis included 74 patients, 36 in the liver transplant group and 38 in the chemotherapy-only group. In this analysis, the 5-year overall survival rate was 73% in the transplant group and 9% in the chemotherapy-only group (HR, 0.16; P < .0001).

Of the 36 patients in the liver transplant group, 26 (72%) experienced disease recurrence: 14 patients had disease recurrence in the lungs, 3 in lymph nodes, 1 in the liver, and 8 in other or multiple sites. Of the patients whose disease recurred, 12 (46%) underwent surgery or ablation, and 15 of 36 (42%) had no evidence of disease.

In contrast, all but one patient (97%) in the per-protocol chemotherapy group experienced disease progression, and only one patient (3%) remained free of signs of disease after switching to a new chemotherapy regimen.

In a per-protocol analysis, the 3- and 5-year progression-free survival rates in the liver transplant group were 33% and 20%, respectively, compared with 4% and 0%, respectively, in the chemotherapy group (HR, 0.34; P < .0001).

These data suggest that “transplant patients with colorectal liver metastases have survival rates comparable to those receiving transplants for established indications for liver transplantation,” said Adam, head of the Hepatobiliary Surgery, Cancer and Transplantation Department at Paul Brussus Hospital in Villejuif, France.

“These results support liver transplantation as a new standard option that has the potential to change medical practice,” Adam added.

Session discussant Lee agreed that the study shows that liver transplantation may lead to improved survival in patients with unresectable colorectal liver metastases.

However, Dr. Lee noted, “Identifying candidates can be difficult.” Overall, 40% of patients submitted were deemed ineligible, and 19% (9 of 47) of patients randomly assigned to transplant did not receive a transplant due to progressive disease or intraoperative findings.

The data shows “how difficult it is to select the right patients” for transplants, Lee said, and questioned whether it would even be possible to develop a standard algorithm to get patients into transplants “when you have such a diverse patient population.”

This study received no commercial funding. Adam and Lee have no relevant disclosures.