Presented by Prof Eric Van Cutsem (University Hospitals Leuven, Belgium)
The TRANSMET study, initially presented at ASCO, provided new data on liver transplantation for patients with liver metastases from colorectal cancer. This randomised study included patients who had not experienced disease progression and had no extrahepatic disease. These patients were divided into two groups: one continued with chemotherapy, while the other underwent liver transplantation. The findings highlighted a significant survival benefit for patients undergoing liver transplantation compared to those continuing chemotherapy. The five-year survival rates for patients receiving liver transplants were notably better. Additionally, the survival rates for these patients were similar to those transplanted for other indications, emphasising the efficacy of liver transplantation in this context. This study is considered practice-changing despite involving a small and highly selected subgroup of patients. The results of this study are likely to spark discussions in various countries regarding the prioritisation and availability of livers for transplantation in patients with metastatic colorectal cancer. Nonetheless, the study, involving participants from France, Italy, and Belgium, underscores the potential benefits of liver transplantation in carefully selected patients with liver metastases from colorectal cancer.
New data from the CheckMate 8HW study were presented on the treatment of metastatic colorectal cancer in patients with MSI-H tumours. This first-line treatment study randomised patients into three groups: standard chemotherapy, a chemotherapy doublet with a biological agent, and two experimental arms—one with nivolumab alone and another with a combination of nivolumab and ipilimumab. So far, the results comparing the nivolumab and ipilimumab combination (NIVO-IPI) to chemotherapy have been released. The comparison between nivolumab alone and the combination treatment is still pending due to an insufficient number of events. The initial data presented at the last ASCO meeting demonstrated that PFS was significantly better for patients treated with NIVO-IPI compared to those receiving chemotherapy. Dr. Lonardi presented new data on the quality of life for patients undergoing these treatments. As expected, double checkpoint inhibition with NIVO-IPI also improved health-related quality of life. This improvement can be attributed to two main factors: the high efficacy of the regimen and its manageable safety profile. Despite the combination treatment causing slightly more toxicity than nivolumab alone, it was generally well tolerated. The study used EORTC questionnaires and other tools to assess various aspects of quality of life, including the general condition and performance status of patients. Results showed consistent improvements in these parameters throughout the study, underscoring the potential benefits of NIVO-IPI in managing metastatic colorectal cancer in patients with MSI-H tumours.
Dr Michel Ducreux presented the SOREGATT study, a study on chemorefractory colorectal cancer patients. The study focused on two treatment sequences: trifluridine/tipiracil followed by regorafenib and the reverse sequence. This randomised phase II study is significant for its analysis of PFS, though overall survival data is still pending. The study demonstrated that the sequence starting with trifluridine/tipiracil followed by regorafenib resulted in better progression-free survival compared to the reverse order. This research is particularly relevant as it started before the results of the SUNLIGHT study were available. The SUNLIGHT study showed that adding bevacizumab to trifluridine/tipiracil significantly improved outcomes compared to trifluridine/tipiracil alone. Given the SUNLIGHT study findings, the current logical treatment approach for chemorefractory colorectal cancer includes trifluridine/tipiracil plus bevacizumab, followed by a tyrosine kinase inhibitor (TKI). Potential TKIs include encorafenib or fruquintinib, the latter of which was recently approved by the FDA and EMA for this indication. The results of Dr Ducreux’s study support this sequence, emphasising the effectiveness of starting with trifluridine/tipiracil with bevacizumab and then moving to a TKI-like regorafenib.
The final data of KEYNOTE-585 were also presented. KEYNOTE-585 focused on patients with locally advanced, non-metastatic stomach cancer. These patients were randomised to receive either perioperative FLOT alone or FLOT combined with pembrolizumab. According to prior reports, the study did not meet its primary endpoint and was deemed negative, although there was a trend toward benefit with the addition of pembrolizumab. Specifically, there was no significant survival benefit observed for patients who received FLOT plus pembrolizumab compared to those who received FLOT alone. In this trial, pembrolizumab was administered for two months before surgery and continued for two months postoperatively during chemotherapy, with a total treatment duration of one year. Despite the lack of a survival benefit, the study did show an advantage in one of its key secondary endpoints: tumour regression. More patients in the pembrolizumab arm achieved a complete histologic response, with a difference of 10-12% compared to those who received chemotherapy alone. However, this improvement in tumour regression did not translate into different outcomes in terms of survival or other long-term benefits as already presented at previous meetings.
The last study discussed was the Armani study, an Italian randomised trial involving patients with metastatic gastric cancer. Initially, these patients received three months of platinum-based chemotherapy. After this period, those without disease progression were randomised to either switch to a maintenance therapy regimen of paclitaxel plus ramucirumab or continue with the same chemotherapy, eventually dropping oxaliplatin and continuing with fluoropyrimidine alone. The findings from the Italian investigators highlighted that the switch to maintenance therapy (paclitaxel plus ramucirumab) significantly improved outcomes. Patients who received this switch maintenance therapy experienced longer progression-free survival and better overall survival compared to those who continued with the initial chemotherapy regimen. Additionally, this presentation included an analysis of various biomarkers, recognising the rapidly expanding biomarker field in gastric cancer. The study examined HER2 status, PD-L1 expression, and other biomarkers to determine if any specific subgroups derived greater benefit from the switch maintenance therapy. The results indicated that no particular biomarker subgroup benefited more than others, suggesting that the switch maintenance therapy with ramucirumab offers a broad benefit to patients compared to continuing the initial treatment after three months
References:
Gelli M.. et al., ESMO GI 2024, abstract #1O
Lonardi S.. et al., ESMO GI 2024, abstract #2O
Ducreux M. et al., ESMO GI 2024, abstract #3O
Shitara K. et al., ESMO GI 2024, abstract #4O
Randon G.. et al., ESMO GI 2024, abstract #5O
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