NICE appraisals on chronic phase CML

Summary of appraisals
The FAD (Final Appraisal Determination) for first line therapy of chronic phase CML has recently been published by NICE. This considers the use of dasatinib, nilotinib and standard-dose imatinib for first line treatment in England and Wales. Nilotinib is now approved for use as a first line treatment as long as the Patient Access Scheme (PAS) offered by Novartis is applied. Dasatinib was not found to be cost effective in part because no similar PAS was forthcoming. It remains uncertain whether BMS will introduce such a scheme in due course - discussions continue. Imatinib continues to be approved.
The approval for use of nilotinib is positive news in ensuring an increase in choice for CML patients for first line treatments. Nilotinib was approved following the introduction of a Patient Access Scheme, which significantly reduces the price of the drug which is of course good news for NHS budgets.
NICE previously approved nilotinib as a second line treatment for patients intolerant or resistant to imatinib (again, through a Patient Access Scheme). Dasatinib (no PAS available) and high dose imatinib were not approved in second line. Nilotinib has been approved for use by the Scottish Medicines Consortium for first and second line use.
What does this mean for SPIRIT 2?
We believe that SPIRIT 2 should continue to be one of the treatment options offered to patients.

Although PCR response rates are higher with nilotinib (ENESTnd study) and dasatinib (Dasision study) than with imatinib, there is no significant difference in survival at three years so the newer TKIs have not been proven to be 'better'. The NICE opinion confirms that nilotinib is 'just as good' and, because of the Novartis PAS, not dissimilar in price and therefore affordable.

Imatinib will be off patent in 2015 (and therefore cheaper) and is likely to remain a mainstay of therapy in the NHS because of superior cost effectiveness when re-evaluated at that point. Imatinib has proven to be highly effective in most CML patients over many years. We need to work out how best to use it.

We therefore need a framework of on-going evaluation (SPIRIT 2) to assess these questions carefully.

If patients fail imatinib or dasatinib in SPIRIT 2, they can now readily access second line nilotinib via the NHS giving a broader range of treatment options than if not in the trial.
The CML Working Group are planning a new first line trial at present (you guessed it… SPIRIT 3), that would incorporate nilotinib and would also address the question of how to reduce dose and/or stop TKI therapy safely in the longer term. Aiming to be open in 2013.

It is therefore more important than ever to put CML patients into trials so that we provide the best evidence-based care for our patients, the best value for money for the NHS and are not unduly seduced by what are still very early data with the newer agents. Thanks to all your hard work and commitment, SPIRIT 2 is recruiting better than it ever has - e.g. 29 patients in February. We have 663 patients at present and should recruit the total of 810 in the next nine months.

What about supplies of dasatinib for patients in SPIRIT 2?
Dasatinib can still be accessed free of charge by patients through entry to SPIRIT 2. All patients randomised to the dasatinib arm of the study are guaranteed supply of dasatinib (at no cost to the NHS) for at least five years after recruitment of the last patient to the study (at present projections this will guarantee supply for all SPIRIT 2 dasatinib patients until at least 2018). This provision alone will save the NHS about £47M (saved from not using imatinib in 405 patients randomised to dasatinib). The NICE guidance makes clear that patients already on dasatinib should continue to receive the drug for as long as it confers benefit. We're seeking clarification from NICE about newly-enrolled SPIRIT 2 patients but it seems likely that ongoing dasatinib (and of course imatinib) supplies will be available to patients in SPIRIT 2 beyond 2018.
We've tried to make the case for ongoing recruitment into SPIRIT 2 and we think it should be one of the options offered to new CML patients alongside 'off trial' imatinib or nilotinib. We're always very keen to hear your views on this and any other aspects of the trial: please feel free to contact us (the SPIRIT 2 Study Management Committee).
Steve O'Brien
Corinne Hedgley
Richard Clark
Jane Apperley

Last modified: Fri, 20 Jan 2017 14:31:39 GMT