NICE recommend rejecting degarelix for acute metastatic prostate cancer

Roger-Kirby,-MRI-imaging-videoYour action is required urgently!
 
Most unfortunately, NICE has recently recommended that degarelix should no longer be approved for use in patients presenting acutely with metastatic prostate cancer (a group within its current licensed indication). As a clinician I have often been faced with patients presenting as an emergency with painful bone metastases, ureteric obstruction, lymphoedema, systemic signs of cancer, very elevated PSA, spinal cord compression, liver failure and other complications of metastatic prostate cancer.
 
Currently, I only have one good clinical solution to these problems (the LHRH antagonist degarelix) and this is the option that we have always used in the past. If this decision by NICE  becomes final, we are faced with having to use sub-optimal therapies (either postponing treatment until the anti-androgen and LHRH agonist kick in or bilateral orchidectomy) for these life-threatening instances. These are far from satisfactory and may actually be dangerous to our patients, and may lead to us being criticised as clinicians.
 
It is very disappointing that NICE is basing this decision on cost rather than clinical benefit, an outcome that leaves us doctors and our patients at considerable jeopardy.
 
What are your thoughts on this draft guidance? Can you think of examples where degarelix has proved to be the most effective option in acute metastatic prostate cancer? Please add your own views to this blog.
 
If you feel strongly about this, please follow this link to register your position on the ACD with NICE:
Comments (17) Add yours ↓
  1. Dominic Hodgson

    It’s disappointing that this is being proposed, since we would like to have an LHRH antagonist available for men presenting as Roger describes. However, a remit of NICE is to seek value for money for the NHS. We have heard today (BAUS, Manchester) of a predicted £5 billion defecit for specialist services. Unless, as a country, we opt to spend more on healthcare, such decisions will be increasingly made. An alternative solution, of course, would be that pharmaceutical companies reduce the cost of their products,

    June 17, 2015 Reply
    • Roger Kirby

      Thanks Dominic. Remember that there is a genuine need for this therapy for the group of patients I have highlighted, the cost of therapy at list price is in fact £1500 a year (and this will also save costs from other interventions, hospitalisation etc) and that compared with enzalutamide is pretty minimal (£2000 a month for that new medication). I also understand that Ferring do offer a significant discount which drops the price considerably which has been approved by SMC and AWMSG and is also available in England. However they were not allowed to submit a PAS as part of the submission to NICE so that organisation didn’t take account of that. I don’t think this is about cost. In fact, I find it hard to understand the rationale for NICE’s stance on this. Can anybody explain it to me?

      June 18, 2015 Reply
  2. Hugh Gunn

    This is a perverse ruling after all of the appeal process it is even worse that the original.
    Degarelix should be available to any patient who presents with high volume advanced (metastatic) disease who will benefit from immediate therapy with rapid reduction to testosterone and will avoid catastrophic consequences of any tumour flare eg spinal cord compression. It is not a cure for spinal cord compression, but a preventative measure and as shown in the manufacturers evidence, highly successful.

    As a patient, spinal cord compression is the worst possible fear and anything that can be done to prevent it should be used. As far as cost goes, the treatment of spinal cord compression far out weighs the cost of degarelix and as far as the patient goes, spinal cord compression should be avoided AT ALL COSTS

    June 18, 2015 Reply
  3. Simon Brewster

    It’s a weighty document which takes in all available evidence and very reasonable expert opinion, but then throws the baby out with the bathwater.

    While the current evidence for superiority of degarelix over LHRH-analogues in terms of time to disease progression and cardiovascular disease risk is not above criticism, the comparative rapidity in achieving castrate testosterone (without testosterone flare) is clearcut. The potential advantage of this for patients with spinal cord compression is recognised by NICE, but instead of supporting the use of degarelix in this small group of patients, the focus is on the difficulty identifying patients “at risk of” SCC and therefore the potential for over-use of degarelix and unnecessary cost.

    A great shame really, BAUS will make a submission in support of use in the oncological emergency presentations SCC and ureteric obstruction. Ferring should have time before the drug goes off-patent (2027 I believe) to gather better evidence for long-term use across the board, or alternatively reduce the NHS price.

    June 18, 2015 Reply
  4. Matthew Bultitude

    I agree with comments above. Does seem ridiculous to me as the only drug of that class that is available. And whilst clearly costs are an issue in the NHS, at £1500 a year when many approved cancer drugs cost far more than that per month (abiaterone in the BNF is £2930 per month!) actually doesn’t seem that expensive for the benefit it gives (immediate testosterone suppression; avoidance of testosterone flare; no need for anti-androgen).

    Is this really all based on cost or is there something I am missing ?

    June 18, 2015 Reply
  5. Robyn Webber

    This is very disappointing news from NICE. As I write this I am not clear as yet as to whether NICE’s ruling will also be applied in Scotland (where I work) or south of the border only.

    Again I want to emphasise the issue of spinal cord compression, which can be potentially catastrophic for the patient, and expensive to treat. Surely it makes more sense to be able to provide effective prevention, then to have to deal with the consequences? Given the options of Degarelix vs emergency treatment for spinal cord compression, not to mention the physiotherapy and rehabilitation required if symptoms of cord compression become manifest surely Degarelix represents value for money?

    Benjamin Franklin said ‘An ounce of prevention is worth a pound of cure’ – advice that NICE should think on.

    June 18, 2015 Reply
  6. Lawrence Drudge-Coates

    This is truly a misguided decision for a stage in prostate cancer where prompt symptom management is essential and reduction in subsequent complications are key.I have treated many men and have seen significant symptom reduction in relatively short periods of time with notable improvements in quality of life.

    This drug makes a difference and should remain part of our treatment arsenal. Hormonal manipulation remains our first line approach and we are duty bound to use the best treatments we have.

    June 18, 2015 Reply
  7. Damian Greene

    I think this is a very poor decision by NICE which will restrict access to a very useful drug which I have used with success for many years.NICE has been wrong in its decisions before in other specialties, but it is most disappointing to have restrictions placed on a drug that is very useful in the emergency situation, particularly in patients with impending spinal cord compression. Cost is always an issue but it is the patients who will ultimately pay the price for this poor decision.

    June 19, 2015 Reply
  8. Philip Cornford

    The need for rapid onset treatment for men presenting with symptomatic metastatic prostate cancer can’t be over emphasised. Unless we want to go back to emergency orchidectomy for these unfortunate men it is important that NICE reconsiders the use of this drug for this subgroup of patients

    June 19, 2015 Reply
  9. Heather Payne

    I hope that NICE will reconsider this decision as there is a real need for men with high risk advanced prostate cancer to have immediate therapy. The data supports the use of degarleix for this group and is essential for those men at risk of catastrophic consequences from tumour flare.

    June 20, 2015 Reply
  10. Ben Challacombe

    I do think this is a really poor decision by people who should have been better informed. It is a drop in the ocean in terms of cost when compared with many other agents and has a genuine clinical use that all urologists and oncologists will encounter every year. What were they thinking?!

    June 21, 2015 Reply
  11. Derek Rosario

    I agree completely with all that has been said.
    The perverse outcome of the appeal is mind-boggling.
    The real problem with the costs discussion is the sensitivity of the ICER to the denominator i.e. how QALYs are calculated – this makes a huge difference to the final decision, which seems bizarre as no confidence intervals are applied.
    To clinical benefit is obvious to all. I hope BAUS can be persuasive.

    June 22, 2015 Reply
  12. Sanchia Goonewardene

    This takes away a really valuable tool in our armamentarium – one which will have significant impact on patient care and treatment options available to them. The patient should be the centre of our world, not cost.

    June 22, 2015 Reply
  13. Stuart Lees

    Fortunately, not a common occurence, but we do have on occasions patients who present with acute symptoms related to metastatic disease and Degarilix is a useful drug to utilise in these specific patient cohorts. The cost of treating complications, SCC, et al, not to mention the emotional and psychlogical effects of metastatic disease in these patients far exceeds the cost of having such a drug available if required in my opinion. Dissapointed, yes. If it was a member of my family, bloody annoyed!!

    June 25, 2015 Reply
  14. Mike Kirby

    This is very unfortunate as we commonly see patients with ureteric obstruction and other signs of locally advanced and metastatic disease that need urgent treatment.
    Orchidectomy is not popular with patients and LHRH agonists need antiandrogen Rx prior to initiation.
    We also need to bear in mind that many men with prostate cancer carry a portfolio of CVD risk factors that increase cardiovascular risk, and many have pre-existing cardiovascular disease. These factors increase the risk of death and this is compounded by impact of ADT on factors affecting cardiovascular risk.
    There is accumulating data on the relationship between ADT and cardiovascular events.
    ADT adversely affects traditional CV risk factors, Obesity, insulin sensitivity, serum lipoproteins,loss of testosterone may increase aortic stiffness, adversely affecting CV risk.
    In addition, testosterone may directly affect cardiac contractility and lead to systemic vasodilation.
    The adverse physiological effects of ADT may therefore increase the risk of thrombo-embolic events.
    ADT may result in increased arterial wall thickness and/or endothelial dysfunction, which in turn may promote formation of atherosclerotic plaque.

    There is early data that over one year of treatment, when patients with a history of CVD at baseline were treated with degarelix, have a significantly lower probability of a CV event or death than those treated with a LHRH agonist
    Ref: Men in need of ADT, especially those with a history of CVD, may have a significantly lower risk of CVD sequelae with the GnRH antagonist, degarelix, compared with a LHRH agonist
    Albertsen P et al. Eur Urol 2014 Albertsen P et al. Poster 781. AUA 2013

    Additional data from a German Health Insurance registry of patients treated with ADT for prostate cancer, including
    10,554 patients treated LHRH agonists
    132 patients treated with degarelix.
    5.9% of prostate cancer patients experienced a CV event (heart attack or stroke)
    The incidence of CV events was 7.8% in the ADT group and 2.3% in the GnRH antagonist group
    Comparable with the rate observed in age-adjusted non-prostate cancer patients (2.37%)CV events in the degarelix group occurred exclusively in patients with high CV risk
    This suggests that the type of ADT is an important factor for risk of CV events in this patient population
    The authors concluded that GnRH antagonists might lead to a lower risk of CV events compared to LHRH agonists
    Ruessel C, Guthoff-Hagen S, Donatz V. Androgen deprivation therapy (ADT) and cardiovascular (CV) risk: Analysis of German Statutory Health Insurance (SHI) data (ASCO GU 2015, Abstract 219)
    I hope NICE will take this into consideration.

    June 26, 2015 Reply
  15. Simon Chowdhury

    A strange and poor decision. This is a small group of patients but an important one where immediate testosterone suppression is essential. As eloquently put by Robyn and Franklin above, prevention especially of cord compression is essential here. Drug costs are easy to highlight but the ongoing costs of symptomatic metastatic prostate cancer are large and ignored. Let us keep our patients well for as long as possible and able to contribute to society in the many ways they do!

    June 28, 2015 Reply
  16. Roger Kirby

    After a rather tortuous and protracted process, NICE have finally approved degarelix (Firmagon) for use in men with spinal metastases from prostate cancer. The TA is now final and has been published on the NICE Website:
    Published : TA 404
    https://www.nice.org.uk/guidance/ta404
    This is good news for urologists and their patients.

    August 24, 2016 Reply

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