SUCCEED trial: Maintenance treatment in advance soft tissue sarcoma

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Published: 18 Jun 2012
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Dr Jean Yves-Blay - University Claude Bernard, Lyon, France

Dr Jean Yves-Blay talks to ecancer about maintenance treatment in advance soft tissue sarcoma at the ASCO 2012 Annual Meeting, Chicago.


The SUCCEED trial’s goal was to increase progression free survival using maintenance therapy with standard chemotherapy in patients after four to six cycles of chemotherapy.


Often patients stop receiving chemotherapy once they start to respond well to treatment as to prevent adverse side effects; however, patients do quickly relapse. The trial used mTOR inhibitors once patients stopped receiving chemotherapy.


The study found an average improvement of seven weeks of progression free survival. Patients in second through fourth cycles saw a much more significant increase, 40%.

ASCO 2012, Chicago, USA


SUCCEED trial: Maintenance treatment in advanced soft tissue sarcoma


Dr Jean Yves-Blay – University Claude Bernard, Lyon, France


The SUCCEED trial was a randomised phase III trial which explored a very innovative question which was the utility of maintenance treatment in advanced soft tissue sarcoma in response or controlled by cytotoxic chemotherapy. The standard is actually in this situation to continue chemotherapy up to four or six courses and if the patient is doing well, in terms of tumour stabilisation or response, to stop, simply because of cumulative effects of chemotherapy. If we do that we know that most of the patients will relapse afterwards, so the question was can we postpone relapse and hopefully expand survival by doing that, using a different type of treatment, a new class of treatment. So that was the question of the SUCCEED trial which actually attempted to prolong progression free survival using an mTOR inhibitor after cytotoxic chemotherapy in advanced phase soft tissue sarcoma, either in first line, second line or third line. So this was a randomised placebo controlled trial, worldwide actually – a very large number of patients because 711 patients were included and were evaluable. The primary endpoint was progression free survival, so those patients were receiving either ridaforolimus or a placebo with no crossover. Actually the study proved very positive in that progression free survival was very significantly improved in the ridaforolimus arm.


What improvements did you see?


The magnitude of improvement is seven weeks. What is interesting is that probably the magnitude of improvement is not reflected by the differences in the median. We have seen, looking at subgroup analysis, and this is the main message of this here for SUCEED because we have this update and a longer follow-up, that if you look at the population of patients in second or third line, let’s say, in this situation the improvement is actually much more substantial than that, it’s a +40% improvement in progression free survival. And it’s very significant, again, in these stratified subgroups and this which was stratified with also an interesting trend in overall survival. This population of patients is very specific in that actually there are very limited treatment options afterwards, nothing is demonstrated useful afterwards. So we really need to give the treatment as long as possible and we can. So giving this maintenance treatment was proven useful in a large proportion of these patients.


So these are the results presented this year and, beyond that, what it shows that the idea of maintenance of treatment is demonstrated to be useful in sarcoma. That is a big change in this landscape because it wasn’t clear and there were some examples suggesting that but no randomised trial. This is one of the largest ever randomised trials performed in soft tissue sarcoma. So this is very good news for the patients; the next step is, of course, to go to the health authorities to ask for availability of the treatment but scientifically already the results are very interesting.


Could you talk about the complications patients have experienced?


If the drug is approved, that’s very much something which should be considered in these patients. In these patients in particular, considering the side effect profile in patients in second or third line, because taking an oral treatment, as compared to receiving cytotoxic chemotherapy in maintenance, of course makes a big difference in terms of side effect profile.


What have been the results of the trabectedin versus doxorubicin for sarcoma trial?


That’s an interesting study because this is a study which is still on-going so it’s presented as part of studies on-going. We should have the results probably for next year’s ASCO. The concept is actually to adapt the treatment to the nature of the driving molecular alteration in this group of diseases which is sarcoma, which is known to be rare but very heterogeneous in terms of molecular alterations. So translocation in sarcoma represents something like 20% of the patients. This is the first trial ever to explore a specific new treatment in a specific subgroup of patients so this is an important step towards personalisation of the treatment. Personalised treatment is very much talked about but here were are speaking of personalised treatment, even in the context of cytotoxic treatment. Trabectedin is an interesting agent in this perspective because it’s a clear cytotoxic agent but it has a very specific profile. It’s not causing alopecia, for instance, which is extremely important for patients with advanced disease, much more than we thought. The mode of action is probably very specific in that it enables to give a long-term duration of the treatment as compared to the standard doxorubicin based treatment which we have to stop after four or six courses. Here trabectedin is useful for some patients, it can be given very long and can be given also repeatedly which means that once a patient relapses following tumour control, reintroduction with trabectedin can be useful, that is something which has been previously shown in different studies. So here in this trial we’ll have a first attempt to put trabectedin in first line setting versus the standard treatment. So this may well change the practice in the future, hopefully.


How many patients will be enrolled in the study?


About 150 patients will be involved finally with translocation created sarcoma.


What has been your involvement in the screening procedures?


This has been a long-term project actually, what we are looking at is what are the feelings of the patients and the doctors, General Practitioners, about the efficacy and utility of screening procedures; what was the knowledge. What was very much interesting is that the level of scientific knowledge which is that of General Practitioner in the field of screening and the level of knowledge also of patients that were not so clear. So in France there was a strong trend to underuse the screening procedures which were proven to be useful for the patient in terms of improving overall survival and overuse of the screening procedures which were not that well demonstrated. I’m thinking, of course, of prostate screening and everything. So that’s quite a unique attempt in a single country, so that’s representative of the activities now in our country, to show that here we need to better educate the public and the General Practitioners but also that things have been improving over the years. The first studies we performed some years ago showed that the situation was actually worse than what it is now; we have improved in this direction. So that’s quite good news because screening is, of course, what we like to do to improve overall survival.