Dr Cremolini on the Implications of the TRANSMET Trial in Colorectal Liver Metastases

Chiara Cremolini, MD, PhD, associate professor, medical oncology, University of Pisa; president, Gruppo Oncologico Nord Ovest (GONO), Fondazione GONO, discusses the implications of the TRANSMET trial (NCT02597348) evaluating chemotherapy and liver transplantation vs chemotherapy alone in patients with unresectable colorectal liver metastases.

One of the most significant recent developments in the field of colorectal cancer management is the TRANSMET trial, a study focusing on patients with liver-limited disease who were deemed unresectable, Cremolini begins. These patients were evaluated at baseline and again after receiving an upfront chemotherapy regimen. The trial enrolled 94 patients, who were randomly assigned into 2 groups. One group (n = 38) received only chemotherapy, and the other group (n = 36) received a liver transplantation following the chemotherapy, but only if they were confirmed unresectable according to standard surgical criteria, she reports.

The findings of the TRANSMET trial were remarkable, Cremolini explains. The trial demonstrated a significant advantage for patients in the liver transplantation group, particularly concerning 5-year overall survival (OS), which was the primary end point of the study, she says. This OS benefit was even more pronounced in the per-protocol population compared with the intention-to-treat population, according to Cremolini. Specifically, the hazard ratio in the intention-to-treat population was 0.37 (95% CI, 0.21-0.65), underscoring the clear benefit of liver transplantation for these patients, Cremolini emphasizes.

Liver transplantation, which has not traditionally been considered part of the treatment arsenal for patients with metastatic colorectal cancer (mCRC), now shows potential as a valuable treatment option for those with liver-limited disease, she continues. The results of this trial are likely to have far-reaching implications, as they indicate that liver transplantation should be considered during multidisciplinary evaluations of patients with mCRC with liver-limited disease, Cremolini adds.

Incorporating liver transplantation into the treatment of these patients represents a significant shift in how mCRC is managed, she notes. This new approach could offer improved outcomes for patients who previously had limited options, marking a critical advancement in the management of this disease, Cremolini concludes.

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Chiara Cremolini, MD, PhD, discusses the implications of the TRANSMET trial in patients with unresectable colorectal liver metastases.

Chiara Cremolini, MD, a medical oncologist at the Tuscan Tumor Institute in Pisa, Italy, discusses the necessary steps researchers must take to identify molecular markers in metastatic colorectal cancer (mCRC).

Cremolini does not believe any clinical trials based on molecular markers can currently be planned, because researchers have not encountered any with promising results. However, she says it is crucial for there to be a collection of biological samples of patients enrolled in the TRIBE-2 trial, a phase III study that will compare first-line FOLFOXIRI plus bevacizumab followed by FOLFOXIRI plus bevacizumab at progression, to FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab at disease progression.

A final analysis of this study may allow researchers to answer questions regarding molecular markers in mCRC.

Dr. Cremolini on Identifying Molecular Markers in mCRC

Chiara Cremolini, MD, a medical oncologist at the Tuscan Tumor Institute in Pisa, Italy, discusses findings from the phase III TRIBE trial that combined FOLFOXIRI with bevacizumab as a frontline treatment for patients with metastatic colorectal cancer (mCRC).

In the trial, bevacizumab plus FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) demonstrated a median overall survival of 29.8 months compared with 25.8 months with FOLFIRI plus bevacizumab (HR = 0.80; 

 = .030). Furthermore, the median PFS was 12.3 months with FOLFOXIRI plus bevacizumab versus 9.7 months with FOLFIRI plus bevacizumab (HR = 0.77; 

One of the main concerns with the combination of the intensive chemotherapy FOLFOXIRI with bevacizumab was tolerability, explains Cremolini. To counter this, patients received treatment with the combination for 12 cycles over the course of 6 months followed by maintenance 5-FU and leucovorin plus bevacizumab until disease progression. Using this method, the combination was tolerable, Cremolini suggests.

A majority of side effects were observed during the induction period, with fewer adverse events occurring with maintenance therapy, notes Cremolini. During the induction period, FOLFOXIRI was associated with a higher incidence of grade 3/4 diarrhea, mucositis, neuropathy, and neutropenia compared with FOLFIRI.

View more from the 2015 GI Cancer Symposium

Chiara Cremolini, MD, discusses findings from the phase III TRIBE trial that combined FOLFOXIRI with bevacizumab as a frontline treatment for patients with metastatic colorectal cancer.


Chiara Cremolini, MD

Articles

Dr Cremolini on the Implications of the TRANSMET Trial in Colorectal Liver Metastases

Dr. Cremolini on Identifying Molecular Markers in mCRC

Dr. Cremolini on Frontline FOLFOXIRI Plus Bevacizumab in mCRC