1O - Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: Updated results from the randomized TRANSMET trial

Background

Definitively unresectable colorectal liver metastases (uCLM) are still associated with poor long-term survival despite the increasing efficacy of chemotherapy (CT). TRANSMET trial aimed to assess the efficacy of CT combined to LT vs CT alone for patients with uCLM.

Methods

Patients with definitively uCLM from resected BRAF non mutated colorectal cancer, responding to CT (≥ 3 months, ≤ 3 lines) and with no extrahepatic disease, were submitted to an independent experts committee (EC) and randomly assigned (1:1) to receive CT and LT or CT alone. Primary endpoint was 5-year overall survival (OS). Secondary endpoints were progression free survival (PFS) and quality of life (QoL). The trial was designed to detect a 40% difference in OS from 10% (CT) to 50% (CT+LT) (2-sided α level 5% - 90% power).

Results

From February 2016 to July 2021, among 157 patients from 20 centers (3 countries) assessed by EC, 94 (60%) were randomly assigned to CT+LT or CT arm. Median number and maximal diameter of uCLM at diagnosis were 20 (13-25) and 51.5 (37-78) mm, respectively. At randomization, objective response was obtained after a median number of 20 (14-27) CT cycles during 1 (44%), 2 (40%) or 3 (16%) lines. 9 patients (19%) in each arm did not receive the allocated treatment for oncological reasons (CT+LT arm) or unexpected curative procedures (CT arm). In ITT analysis, 5-year OS was 57% in CT+LT arm and 13% in CT alone arm (p 0.0003 - HR 0.37; 95%CI 0.21-0.65). In per protocol analysis, 5-year OS rate was 73% and 9%, respectively (p < 0.0001, HR 0.16; 95%CI 0.07-0.33). Median PFS was 17.4 and 6.4 months (HR 0.34; 95%CI 0.20-0.58), respectively. Among transplanted patients, 28 (74%) had recurrence, optionally treated by surgery (36%) or local ablation (11%). Fifteen (40%) patients were ultimately disease-free. In term of QoL, a trend towards a degradation in the physical functioning dimension and main symptoms were observed in arm C.

Conclusions

Through a selection process which is essential, LT combined with CT significantly improves survival compared to CT alone and may become a new standard option in the treatment strategy of liver-only uCLM patients.

Clinical trial identification

NCT02597348.

Legal entity responsible for the study

Assistance Publique - Hôpitaux de Paris (APHP) University Paris-Saclay, Kremlin Bicêtre, France.

Funding

Funding for this study was acquired from a Clinical Research Hospital Program grant (PHRC-K) from the French Ministry of Health, Institut National du Cancer, and from the French National League against Cancer.

Disclosure

All authors have declared no conflicts of interest.