Trifluridine/tipiracil followed by regorafenib can be an effective treatment sequence in pretreated mCRC
Prof Michel Ducreux - Gustave Roussy Cancer Centre, Paris, France
My study was about the sequence of treatment for patients with advanced metastatic colorectal cancer. We knew in the past that there were two drugs that were able to improve the overall survival of these patients, regorafenib and trifluridine/tipiracil, but we didn’t know what could be the best sequence – to start with regorafenib first or to start with trifluridine/tipiracil first. The aim of the study was to evaluate the two sequences, regorafenib followed by trifluridine/tipiracil or trifluridine/tipiracil followed by regorafenib.
What was the study design?
It was a randomised phase II study, and at the beginning of the study it was planned to include more than 300 patients in the study, but we stopped the accrual following the results of the SUNLIGHT trial showing that trifluridine/tipiracil is more active when it is given in combination with bevacizumab.
What were the results of the study?
The results are very clear. As a sequence, trifluridine/tipiracil followed by regorafenib is a better sequence, with more patients that are able to receive at least two cycles of each drug, 60% of the patients could have that in this arm. At the opposite, patients receiving first regorafenib had some problems with toxicity and it was less easy for them after progression to regorafenib to receive trifluridine/tipiracil. So this is in terms of possibility of doing the two sequences of treatment, but there are also positive effects in favour of trifluridine/tipiracil followed by regorafenib in terms of control of the disease, and particularly in terms of progression free after receiving the two treatments. This is really absolutely no problem. This is really in the advantage of the sequence trifluridine/tipiracil and then regorafenib.
What is the clinical significance of these results?
These results are very consistent with what we obtained after the SUNLIGHT results. It means that now the standard of care for third-line chemotherapy of metastatic colorectal cancer is really trifluridine/tipiracil plus the addition of bevacizumab following the results of SUNLIGHT, and that we have to keep regorafenib for fourth-line when patients have a tumour that is progressing when they receive trifluridine/tipiracil plus bevacizumab.
Is there anything else you would like to add?
No. I think this is a study that gave very, very clear answers. We are working in terms of a transnational approach to try to define the patients that are best benefitting from regorafenib.
