Administering systemic chemotherapy improves survival for patients with resectable CRCLM
Dr Giacomo Bregni - Francis Crick Institute, London, England
At ESMO GI I presented individual patient data meta-analysis about the management of colorectal cancer liver metastasis. As you may know, patients with colorectal cancer liver metastasis can receive surgery and can benefit from surgery on liver metastases, but the risk of recurrence is very high. Because of this, several strategies have been tested in clinical trials adding systemic chemotherapy to the resection liver metastases. Some of these strategies are post-operative only, so we have several trials testing post-operative chemotherapy after the resection liver metastases. At least one of these trials is a perioperative strategy, so giving systemic chemotherapy before and after the resection liver metastasis. We have a total of five randomised phase III trials testing systemic chemotherapy versus control in addition to liver metastasis resection. The fact is, since these trials are pretty limited in sample size, two of them closed early. They’re not big enough to address all the questions we have regarding this setting. The main questions, I would say, are who are the patients benefitting the most from this strategy in terms of disease-free survival and does this strategy, the addition of systemic chemotherapy to the resection liver metastasis, give a benefit in terms of overall survival?
As I mentioned, we have five randomised phase III clinical trials. Three of them were positive in terms of DFS; none of them was positive in terms of overall survival, considering that DFS was the primary endpoint for these studies. To try to clarify these questions, to try to address these questions, we collected individual patient data from four of these five trials. Unfortunately, we were not able to secure the data from the JCOG0603 trial, because it’s still undergoing analysis to clarify some points regarding the results. We collected data from these four trials, three testing post-operative chemotherapy and one testing peri-operative chemotherapy, and we did an individual patient data meta-analysis.
With this meta-analysis, which included 821 patients, we showed that systemic chemotherapy does give a significant DFS advantage in the whole population. So systemic chemotherapy improves DFS in these patients both when we consider all trials combined and when we consider only the post-operative chemotherapy strategy.
There are two subgroups benefitting the most in terms of DFS. These are the patients with synchronous liver metastases or the patients with normal alkaline phosphatase levels. We also observed that this strategy, so adding systemic chemotherapy to the surgical resection metastasis, improves overall survival. This is a very interesting finding, because it’s the first time we are able to show an overall survival benefit granted by one of these strategies.
I would say that the interest of our study lies in confirming the DFS advantage, showing that there are at least two subgroups of patients benefitting significantly from these strategies and showing that, in fact, these strategies can give an overall survival advantage.
Regarding the future, there are two main things related to this study. One is we’re conducting currently a Delphi survey among European experts in different fields. We have medical oncologists, we have surgeons, we have radiologists, we have interventional radiologists, we have pathologists, we have radiation oncologists, and we’re asking them a set of questions about how to best manage colorectal cancer liver metastases. We know that some of these points cannot be clarified for the moment through the availability of data, because we don’t have data on all of the questions that are outstanding, so what we are trying to do is to find a consensus among experts to help guide practice and to help homogenise, a bit, practice across Europe, because for the moment practice is very heterogenous regarding the management of colorectal cancer liver metastases. The second thing is we hope in the future to also gain data from JCOG0603, so to make our individual patient data meta-analysis more complete with all the available data.
