Retreatment of ovarian cancer

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Published: 11 Jan 2011
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Prof Jonathan Ledermann – University College London, UK
Prof Jonathan Ledermann speaks about the change in opinion towards the retreatment of patients with ovarian cancer. Recent studies have shown that the addition of trabectedin to pegylated liposomal doxorubicin therapy can increase overall survival, particularly in women who are partially platinum sensitive. This new treatment regimen is likely to be a useful tool increasing the interval between platinum based therapies and therefore increasing the success rate of these therapies. Prof Ledermann speaks about work being done to identify additional drugs to increase the platinum interval, considers the possibility of developing new treatments for patients resistant to platinum based therapies and discusses developments in targeted therapies.

ESMO 2010


Professor Jonathan Ledermann – University College London, UK


Bevacizumab as part of standard first line treatment of ovarian cancer


We’ve had a very interesting presentation at this ESMO meeting and that is the use of Bevacizumab, the antiangiogenic drug, in the first line treatment of ovarian cancer and the results were presented here and showed, very much like the previous presentation of an American study at the ASCO meeting this year, that the addition of Bevacizumab to standard chemotherapy prolongs the progression free survival. So on the face of it we have a new drug that is extending the progression free survival and that’s certainly a very good thing, but it has raised some questions and these were debated this morning in a controversy session which really asked the question as to whether or not we have a new standard of care and whether this compound, Bevacizumab, should be now routinely used in the first line treatment of ovarian cancer.


What were the arguments for and against the use of Bevacizumab?


The strongest argument in favour of using it is that we’ve seen two studies with a definite prolongation in progression free survival and this benefit seems to be best in the group of women who we would put in a poorer prognostic group, those with larger amounts of disease remaining at the end of their primary surgery. They’re the ones that seem to have had the best extension in progression free survival.


There are a couple of problems though, firstly the data from both the ICON7 study and the GOG study are not yet sufficiently mature to know whether this translates into an overall survival benefit. Of course that is of paramount importance in making decisions about chemotherapy. Having said that, improvements in progression free survival are of course important and what we need to work out is whether the improvement, which is relatively short, is short because the patients haven’t been treated for long enough and whether if you treat patients for a longer period of time you might get greater benefit. So some of the debate today centred around whether or not patients should have prolonged treatment, even going on beyond the time of progression and whether one would get more out of the drug if that were the case.


So the main argument, of course, against doing that is principally a cost argument. There is, of course, some toxicity from the drug; there was nothing new shown in this study but hypertension and some fatigue are side effects of this drug so it all has to be balanced up very carefully.


What was the outcome of this session?


We had a vote both at the beginning and at the end and I think the most striking thing to me in comparing some of the questions which were the same before and afterwards was that the proportion of don’t knows shrank dramatically, which was very good in some ways because it meant that people started to take sides and then some of those questions they sided in favour of incorporating the drug in the first line setting at this stage. Having said that, the majority of the audience felt it was still too early to be definite about incorporating this drug as a standard of care and we need more time, more information about the drug and other studies before we can be certain about that.


One of the other things that was raised in the questioning which I think is worth bringing up, is that the study in the US and in the rest of the world used different doses of Bevacizumab. The ICON7 trial used half the dose and of course that’s important because of cost issues and it does seem that the magnitude of benefit is the same with the lower dose of Bevacizumab.


How long will it be before we can determine if Bevacizumab should be used?


I think it depends on whether the regulatory authorities, both the FDA and the EMA, would accept the progression free survival data as being sufficient for registration and none of us know the answer to that. The overall survival data should be available for both studies around about 2012.


What message should patients take from this?


The difficulty is that the drug is not licensed and in most European countries that creates a problem. It is licensed, of course, in other cancers and there may be situations where patients can obtain the drug off-label but in the main throughout Europe I think it will be difficult to prescribe this drug without patients being enrolled in a clinical trial until the drug is licensed.