2010 American Society of Hematology Annual Meeting 3rd - 7th December

Interview with Prof Carlo Gambacorti-Passerini - University of Milan Bicocca, Italy 

Bosutinib as a treatment for newly diagnosed chronic myeloid leukaemia

IV         Interviewer

CA       Carlo Gambacorti-Passerini

CA        We compared on 502 newly diagnosed CML patient the effect of Bosutinib  given at 500mg daily versus Imatinib as a comparator that's represent the standard treatment for newly diagnosed patient today and we looked at one year follow up in these two groups of patient.  And what we noticed is that the patient on Bosutinib got faster responses, they reached a cytogenetic and molecular response at a time that is almost half that needed for Imatinib.

IV         Tell me a little bit about Bosutinib, will you?  It's a second generation TKI but what potentially should be the advantages?

CA        The advantage of Bosutinib again is the highest potency and the good tolerability of the drug.  We can't speak about adverse events because in fact in the presentation there have been a number of patients that were dropped because of adverse events.

IV         I want to ask you about the adverse events, but you did say there were benefits.  Now, could you carefully run me through those figures, in rough numbers anyway, just what were the differences between the responses you got with Bosutinib and those with Imatinib?   This was a head-to-head study.

CA        So, the response in terms of therapeutic efficacy - as I told you - were faster responses and also a reduced number of patients.

IV         And the figures were what, exactly?

CA        The figures are about half the time that is needed for patients to reach a cytogenetic response in the Bosutinib arm compared to the Imatinib arm and the same for the molecular response.  And also in terms of progression, so patients that failed treatment, that progressed to more advanced form of the leukaemia or that even died because of leukaemia, all this figures show that the numbers have been reduced significantly in the group that is receiving Bosutinib.

IV         By what sort of amount?

CA        About two to three times, so we have like 10% of patients that progressed, that failed treatment in the Imatinib arm, versus just 3% in the Bosutinib arm; so it's like a threefold reduction.

IV         What about the quality or depth of the response?  I mean, molecular response, for instance.

CA        Again molecular responses were observed in approximately 40% of patient at one year.  This number probably are going to increase over time as we increase the follow up of the patient.  And again we had, if you want, a problem of early drop out from patient because of adverse event, but I think we are paying a little bit of a price of Bosutinib not being familiar in the haematological community.

IV         Okay, so now I do want to ask you about adverse events and you're saying that part of this might be unfamiliarity but tell me what the broad figures are so far.

CA        The broad figures are that we had overall 19% of patients that were discontinued because of side effects in the Bosutinib arm.  And the most frequent figure for discontinuation are being increased LFT, so this is something that physicians should be aware of but also they should be aware of that with the proper management probably these numbers are going to be significantly reduced.  But anyway it's important that physician that would use Bosutinib would look carefully at the LFT elevation in their patient and would either treat them accordingly or know about the toxicity because some patient indeed will not be able to tolerate the drug, as it happens with any type of drug.

IV         So you're looking at a promising new agent, a second generation TKI for chronic myeloid leukaemia that's not yet licensed.  This is described as an ongoing Phase III study…

CA        Correct.

IV         What do you advise doctors to make of the figures that you've been quoting here at the American Society of Haematology meeting today?

CA        I have to remember that Bosutinib is an experimental drug so it means that it is not licensed for any indications so far, so it's only available outside clinical trials as part of a compassionate use.  The message that I would give to physicians is that the drug again is quite safe; in my opinion it's probably the safest among the second generation TKIs and it just requires, as for any drug, a familiarity with the use.  Of course, if you use for the first time you need to be careful and to manage the patient properly.

IV         Of course, I should ask you about your thoughts about how it might shape up against Nilotinib and Dasatinib, for example.

CA        Okay.  I think in terms of the efficacy the data are very similar.  They, of course, cannot be compared because they arrive from different studies, but if you look at the numbers of molecular responses, numbers of patients that failed treatment or progressed, the numbers are not dissimilar among the three. 

What is different is the toxicity profile so, for example, we had a very low level of haematological toxicity and that's partly due to the fact that Bosutinib does not inhibit KITA which is instead inhibited by the other TKIs.  We also didn't have some of the side effects that are present with other drugs like pleural effusion or problem in terms of diabetes, pancreatitis or QT elongation and this I think it gives a safety profile which is different from the other drugs and which can be usefully utilised in terms of patient tolerability.  So, for example, it definitely true that if you have a patient with pulmonary co-morbidities with BPCO probably you would not want to use Dasatinib in that patient, so it is important that you have alternatives.

IV         If the learning curve continues and Bosutinib is put on map, very much on the map, do you guess that it could be more helpful in first line therapy or should it be reserved for use when Imatinib fails, do you think?

CA        I think that at present Imatinib has the strong advantage of having the most robust and longest follow up data and I think that this is an important information in order to decide treatment, especially for the newly diagnosed patient that has a quite good probability of response and of having a normal life expectancy.  So in my opinion at present this compound have been, have to be seen as very good alternatives to Imatinib but when anything will not go or flow smoothly with this drug, either in terms of compliance and side effects or in terms of not reaching the optimum treatment milestones.

IV         And the main message that you'd like to convey to cancer doctors at this point?

CA        It's that this field has many options; it's, I think, a privileged field.  In many other fields in haematology and oncology we don't have this option of so many active and safe drugs.  But at present I still think Imatinib is the drug with the strongest background to be used, let's say outside the clinical trial.

IV         Carlo, thank you very much for taking this time off here at the American Society of Haematology meeting.

CA        It's a pleasure.

IV         And thanks for being on ecancer TV.

CA        Okay, thanks to you for inviting me.