DASISION study on cardiovascular safety in patients with CML-CP

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Published: 18 Feb 2011
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Prof Giuseppe Saglio - University of Turin, Italy
Prof Giuseppe Saglio speaks about the DASISION trial which compares dasatinib with imatinib as initial treatment for patients with newly diagnosed chronic myeloid leukaemia in chronic phase (CML-CP). Cardiovascular disease is an important comorbidity in some patients with CML-CP and this study assessed the effect the drugs had on efficacy and safety. Prof Saglio outlines the results of this study and explains the role he believes imatinib and dasatinib have to play in the treatment of CML-CP.

This programme is supported by an educational grant from Bristol-Myers Squibb.

G_Saglio 

 

 

Speaker key

 

IV                     Interviewer

GS                   Giuseppe Saglio - Interviewee

 

 

IV         One of the studies that you’re talking about here is the DASISION study looking at dasatinib.  Tell me about this study would you?

 

GS       The study was focussed just to look at the safety aspect of the dasatinib.  We are particularly concerned with the cardio vascular effects and we know that the cardio vascular effects are quite frequent in the general population.  There are different percentages in different studies where approximately one third of the patients may have cardio vascular problems.  In the decision study which was a phase three comparing dasatinib versus imatinib there were approximately one fifth of the patients, 20% of the patients who had cardio vascular problems including hypertension, diabetes, even previous coronary artery disease and so on.

 

IV         So this is a real world situation?

 

GS       It is a real world situation.

 

IV         And you have patients that may have CML but do you have core morbidities?

 

GS       Absolutely and this is quite frequent of course in the elderly population and indeed these patients had a median age which was a little bit higher than the general population studied in the DASISION trial.  It was very interesting to see the efficacy but also the tolerability of the treatment in this specific group of patients. 

 

IV         You had just over 500 patients.  You divided them between imatinib or dasatinib front line therapy fore their CML?

 

GS       Absolutely.

 

IV         What did you do and what happened?

 

GS       They were treated for CML and they were carefully monitored for the cardio vascular events and also the side effects that they develop.  What we know and it’s very important that imatinib is use in more fluid retention with respect to the disatinib but concerning a specific type.  It’s not a fluid retention but pleural infusion.  We know that this is frequent with Disatinib with respect to Imatinib, and indeed just to be treat with Disatinib increases the risk of developing pleural infusion in the patients with cardio vascular problems with respect to the general population.  However, this does not affect the efficacy and I would say that the side effect is quite manageable because it can be overcome via disruption or discontinuation for a while and other therapy. 

 

IV         You do have some efficacy data from your phase three study don’t you?

 

GS       Of course and they are always showing that there is an advantage in terms of efficacy with dasatinib and with imatinib in terms of cytogenetic remission and also for molecule remission. 

 

IV         So if you’re a doctor in practice looking at CML you may have a number of patients with co-morbidities.  What are the clinical implications coming out of the decision?


GS       It’s not contraindicated in patients with cardio vascular problems if it’s of course in a stable situation with dasatinib 100mg per day.  Of course you must monitor these patients carefully and if there are side effects including pleural infusion you must manage this situation in order not to interrupt for a long period of time the treatment.  But in most of the cases this situation is clinically manageable.

 

IV         Is it better to begin with dasatinib now?  Is that a clear cut question or is there still work to be done.

 

GS       In my opinion the data is quite mature, but of course they are going in the direction of better efficacy of dasatinib.  Of course the full proof of this data will come in the next few years, I would say with longer follow up of at least 2 to 3 years.

 

IV         Could you tell me something about the levels of cytogenetic response rates as compared with molecular response rates with these two agents?

 

GS       Yes, in both cases the difference is a statistical significance in favour dasatinib with respect to imatinib with a difference which is at least for the cytogenetic remission of between 10% and 15%, and in terms of molecular response is even higher.  More than double of patients treated with dasatinib achieve major molecular response with respect to this treated with imatinib. 

 

IV         So how do you see therapy in practice evolving or front line therapy for CML?

 

GS       I think that in most instances second generation TKI will replace imatinib and of course imatinib will be used in patients who cannot tolerate second genertion TKI.  It’s exactly the opposite of what we’re going to see what we are going to do today.  In other specific groups in my opinion this should be a priority with the high risk patients or patients also with intermediate risk.  Of course it’s more a matter of debate if also patients in lower risk groups should be treated with second generation TKI.  This means more time but I think certainly we are moving towards a more aggressive front line therapy.

 

IV         So the exact position, what would you predict the position of dasatinib that you’ve been investigating to be in the therapeutic armoury?

 

GS       I would say it is the first line therapy to be used; of course it will solve most of the problems of the patients.  There will be a group of patients that cannot tolerate the drug and they of course can be moved to other TK inhibitors and there are still very few patients who will progress but certainly less patients will progress under this dasatinib than under imatinib.  What we will see in the future is that although there are more patients we must concentrate our attention on this group of patients because just to be able to beat and to eradicate the disease even in these cases will provide the final solution for this haematherapy. 

 

IV         So eradication?

 

GS       Eradication, yes.

 

IV         So what message would you like to leave doctors with?  What should they be thinking about, busy doctors? 

 

GS       I think that of course the last ten years have been very important since haematherapy because we have been able to transform a chronic disease.  It was called chronic before but it was not chronic it was evolving very rapidly towards an acute phase and now it’s chronic but with very few cases progressing.  We do have to move forward and to try to definitely kill the disease which means also the possibility of discontinuing treatment, sooner or later in most if not all of the patients. 

 

IV         Giuseppe thank you for joining us here on ecancer Television and I look forward to hearing more about this. 

 

GS       Thank you.