The initial data from the '035' first-line dasatinb study were presented at the EHA meeting in Barcelona last weekend (abstract 560) and at ASCO a few days previously. An update on the first-line nilotinib study, ENESTnd, which was initially presented at ASH, was also presented (abstract 1113). It's early days for both these studies: 12 month data were being presented.

In terms of cytogenetic and molecular response at one year, both nilotinib and dasatinib are significantly beter than imatinib and with nilotinib there is a small but significant reduction in disease progression at one year. These studies have both just been published in the New England Journal of Medicine.

Nilotinib: EHA abstract 1113

Dasatinib: EHA abstract 560

Nilotinib: NEJM paper

Dasatinib: NEJM paper

So what's the message?

Well, both dasatinib and nilotinib seem to be better than imatinib in terms of one year response. For example, complete cytogenetic response (CCR) rate with nilotinib was 80% vs 65% with imatinib at 12 months; CCR rate with dasatinib was 77% vs 66% with imatinib at the same time point. Major molecular response rates (BCR-ABL/ABL ratio of <0.1%) were also significantly better with the newer drugs and the nilotinib study showed a decreased rate of progression at one year. So the drugs look very promising but it's early days - we know nothing about comparative long-term survival as yet and, regrettably, there are still no head to head studies of nilotinib and dasatinib.

 

What are the implications for SPIRIT 2?

So does this mean that these two new drugs are so obviously better than imatinib that we should just switch over and close down SPIRIT 2? Probably not. It is too early to say whether these two new drugs are superior to imatinib in terms of longer term survival: responses might be great at one year but what about longer-term tolerability, compliance and efficacy? If patients can't or won't adhere to long-term treatment then survival may be no different than with imatinib. In the UK at least the first-line use of these drugs is purely a theoretical consideration at present as the newer drugs are not licensed for newly-diagnosed CML and would certainly not be paid for in the NHS. NICE are only part way through their appraisals of first line nilotinib and dasatinib (SPIRIT 2 is expected to be a major part of this) and it will be at least 2011 before their initial opinion is forthcoming. It seems very unlikely that they will allow first-line use in the NHS with such immature data.

 

It is of course in the interest of the drug companies to get their drugs to market quickly in order to recoup their development costs but as responsible clinicians I think we have a duty not to be too hasty to adopt therapies that have not stood the test of time. Now more than ever a careful long term evaluation of these exciting but as yet unproven (and expensive!) 2nd generation TKIs is essential. Which is why I would ask you to continue your tremendous support for SPIRIT 2 and put patients in the study. NICE will then hopefully have the longer-term data they need to make a careful assessment of their worth to our patients and the NHS and allow us to make solid progress in the treatment of CML.

 

We'll be bringing you some more CML news from EHA over the next few weeks.

Steve O'Brien

Chief Investigator, SPIRIT 2