Download Degarelix for advanced hormone dependent prostate cancer

Degarelix for advanced hormone dependent
prostate cancer
South West Peninsula checs assessment
Commissioning Decision
(made by the Peninsula Health Technology Commissioning Group)
Clinical case: Equivocal
Cost-effectiveness case: Restricted cost-effectiveness
Commissioning decision: This treatment will not be routinely commissioned
Date issued: March 2010
Rationale for Commissioning Decision
A clinical trial has demonstrated that degarelix reduces testosterone to
similar levels over one year of treatment compared to current therapy with
gonadorelin analogues. This is accepted as a measure of achieving similar
disease control. There are no data on which to make a judgement on longer
term survival.
The Group accepted that there is no initial, short-term rise in testosterone
levels upon initiation of degarelix therapy, unlike the situation that occurs on
initiation of gonadorelin analogues. There are currently no data
demonstrating a reduction in clinical events occurring around the time of
initiation of therapy compared to gonadorelin analogues.
The Group considered that there was insufficient evidence of clinical benefit
compared to current standard therapy with gonadorelin analogues on which
to base a case for its use at a price that is greater than that of the
gonadorelin analogues.
NOT TO BE USED FOR COMMERCIAL OR MARKETING PURPOSES.
PRODUCED TO INFORM LOCAL DECISION MAKING.
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checs assessments
checs (Clinical & Health Economic Commissioning Support) assessments are produced by the
operations team of the Peninsula Health Technology Commissioning Group co-ordinated through NHS
Devon.
This NHS initiative was set up to provide commissioners with high quality evidence in the form of
health technology assessments of clinical evidence and cost effectiveness to support local decision
making.
checs assessments provide

Rapid access to the results of health technology assessment.
Assessments are produced for medicines and indications for which there is
no NICE Technology Appraisal Guidance.

Assessments that are based on published information and NHS
clinical expertise. The process does not include submissions from
pharmaceutical companies

Concise reports clearly stating the outcome of the clinical and costeffectiveness assessments and the rationale for the commissioning decision
in the South West peninsula

The estimated price at which medicines may be cost-effective. Enabling
commissioners to explore ways in which value-based pricing can be
achieved at the local or regional level for medicines which are clinically
effective but not cost-effective
Support for the cost effectiveness analysis has been provided by PenCLAHRC at the Peninsula
College of Medicine and Dentistry (Universities of Exeter and Plymouth) through work partially funded
by the National Institute of Health Research (NIHR). This collaboration gives the local NHS access to
a broad range of expert resources in health technology assessment including researchers with
experience of producing assessments for NICE. A review of the clinical evidence is undertaken by the
clinical effectiveness team within Public Health of NHS Devon. Clinical aspects related to the
treatments are discussed with clinicians involved in the care of patients.
Publication of the original research undertaken for these assessments is sought in peer reviewed
journals. checs assessments are made available in advance of this to assist other NHS bodies in
their decision making.
The authors have no competing interests to declare
Peninsula Health Technology Commissioning Group
The Peninsula Health Technology Commissioning Group is a collaborative commisisiong arrangement
of the four PCTs in the South West peninsula (NHS Cornwall & Isles of Scilly, NHS Devon, NHS
Plymouth and Torbay Care Trust). The commissioning group takes decisions on the commissioning of
treatments on behalf of the constituent PCTs. These decisions are made after consideration of the
clinical and cost effectiveness of the treatment, the financial impact and comments made in clinician
and patient group submissions. Membership of the group is drawn from a wide array of local
stakeholders including clinicians, public health, PCT commissioners, lay members and academics.
The decisions of the Peninsula Health Technology Commissioning Group are available at :
http://www.devonpct.nhs.uk/SWPHTCG/SWPHTCG_Commissioning_decisions2.aspx
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Executive Summary

Degarelix is a type of hormone therapy for use in advanced prostate cancer. It
acts by blocking the gonadotropin releasing hormone (GnRH) receptor
producing a rapid reduction in testosterone and prostate specific antigen (PSA)
and avoids the initial testosterone surge (‘flare’) associated with luteinising
hormone releasing hormone analogues (LHRHa).

Current standard treatment is to use a luteinising hormone releasing hormone
analogue (LHRHa) such as triptorelin, goserelin or leuprorelin, plus oral antiandrogens commenced a few days before the LHRHa and continued for about
three weeks to block the effects of the ‘flare’.

There is evidence from one open-label, randomised, controlled trial
demonstrating that degarelix reduces testosterone to similar levels over one
year of treatment compared to current therapy with LHRHa therapy with
leuprorelin.

No evidence was found that readily provided characterisation of biochemical
measures and clinical events related to testosterone flare. The clinical benefit
of avoidance of tumour flare with degarelix has not been assessed in clinical
trials as an outcome measure.

The manufacturer’s submissions to the Scottish Medicines Consortium (SMC)
and All Wales Medicines Strategy Group (AWMSG) in 2009 were not accepted
due to weaknesses in the health economic models. In January 2011 the SMC
published an acceptance of a resubmitted case. The cost utility model
supporting this was based upon secondary endpoint data of PSA recurrence
derived from a one year study and interim results from an extension phase
extrapolated over 20 years. In this model the increased drug cost of degarelix
were offset by reduced costs of more expensive therapy incurred upon disease
progression. Goserelin was the comparator used in the model, whilst leuprorelin
was the comparator used in the trial. The acceptance is contingent upon the
availability of a discounted price for degarelix, the detail of which was not
revealed by the SMC.

Triptorelin is recommended in formularies across the Peninsula and is cheaper
than the goserelin used in the SMC/AWMSG model and was used as the
comparator in our model.

The European Medicines Agency identify that the major clinical added value of
degarelix is the avoidance of testosterone flare upon initiation of treatment. The
Summary of Product Characteristics for degarelix clearly states that data on
clinical experience of efficacy and safety is limited to one year.

We present a decision analytic model (consisting of a decision tree and a
Markov submodel), to estimate the cost effectiveness of degarelix compared to
triptorelin plus short term anti-androgen cover in the management of patients
with metastatic prostate cancer. The model focuses on the costs associated
with the serious complications (spinal cord compression and bladder outlet
obstruction) of testosterone flare which occurs on initiation of LHRHa therapy.
These outcomes have not been assessed in clinical trials of degarelix but the
absence of biochemical flare has been demonstrated. This model assumes that
the long term effects of degarelix and triptorelin on prostate cancer are
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equivalent and therefore assesses the cost effectiveness of the short term
proven biochemical advantage.

In the base case scenario, the ICER for degarelix compared to triptorelin plus
anti androgen was £59,000 per QALY gained.

A sensitivity analysis was undertaken to examine all of the uncertainties of the
data. The model suggests that the biggest sources of variation to the cost
effectiveness case are the price of degarelix, the rate of progression of the
disease, the proportion of patients who suffer spinal cord compression on
initiation of LHRH therapy, and the proportion of cases of SCC that are severe.

The ICER was very sensitive to the price of degarelix. If the price was 70% of
the market price, degarelix dominated, i.e. it produces more QALYs and incurs
less total costs compared with triptorelin plus anti-androgen.

Clinicians identified the following subgroups in which additional benefit with
degarelix over an LHRHa may be present
o patients at high risk from a clinical flare
o patients presenting with spinal cord compression or bladder outlet
obstruction.
We found no suitable evidence permitting quantification of any benefits in these
specific subgroups and hence our model is restricted to the general population
of men with metastatic prostate cancer

This assessment demonstrates that at the UK list price, degarelix does not
represent a cost effective use of NHS resources. If the price of degarelix were to
be reduced by 30% it might reduce overall NHS costs associated with hormonal
treatment of advanced prostate cancer, but there is much uncertainty in the
clinical data. Even at this price the drug acquisition cost is greater than
alternative treatment with triptorelin. These results support the SMC position
that degarelix should only be used if a discount scheme is available, but the
details of this scheme have not been made publically available. It is up to
individual commissioning organisations to determine if any scheme offered is
acceptable, giving consideration to drug acquisition cost and the administrative
cost and burden of operating the scheme.
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Abridged Heath Technology Assessment
1.
The Technology
Degarelix is a new treatment for advanced hormone dependent prostate cancer. It
presents a novel form of hormone manipulation by blocking the gonadotropin
releasing hormone (GnRH) receptor leading to a rapid reduction in testosterone and
prostate specific antigen (PSA).
The current standard treatment is to use an analogue of luteinising hormone
releasing hormone (LHRHa) such as triptorelin, goserelin or leuprorelin. These
types of treatments produce an initial, short-term stimulation of testosterone release
followed by a reduction to castrate levels within 1 month. The initial stimulation,
which typically occurs within the first few days of treatment and persists for about a
week, is called a ‘flare’. This biochemical ‘flare’ may be accompanied with clinical
symptoms. Current practice, supported by NICE guidance and BNF
recommendation is to commence therapy with oral anti-androgens a few days
before initiation of the LHRHa and continue for about 3 weeks to block the effects of
the flare. However, there is a lack of conclusive evidence to support the clinical
benefit of the routine application of this prevention strategy.
Degarelix does not initially stimulate testosterone production. As there is no
biochemical flare, the prescription of anti-androgens is not required.
2.
The clinical need
Prostate cells are dependent on androgens, such as testosterone, to stimulate
growth. As most of the circulating testosterone is derived from the testes, prostate
cancer growth can be slowed by surgical castration. Medical castration with
LHRHa hormone therapy is a well established alternative option in the management
of prostate cancer, which many men find more acceptable.
The initial stimulation of testosterone release brought about by LHRHa therapy can
produce troublesome symptoms such as bone pain. More serious complications are
comparatively rare but can include urinary obstruction and spinal cord compression,
which may lead to permanent disability.
Due to its mechanism of action, degarelix does not cause this testosterone flare.
This has been identified as the significant clinical advance of interest for patients
with metastatic disease. Data for England suggests that 8.5% of new presentations
of prostate cancer have metastatic disease (British Association of Urological
Surgeons). In 2007 there were 1,249 new registrations of prostate cancer in the
South West Peninsula.
3.
Strategic direction
There is no NICE technology appraisal of degarelix, nor is one planned. Initially the
Scottish Medicines Consortium (SMC) recommended that degarelix not be used in
NHS Scotland as the economic case was not sufficiently robust. This decision was
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reversed in January 2011 after a resubmission. The All Wales Medicines Strategy
Group have recommended that it is not used in Wales as the case for cost
effectiveness has not been proven.
NICE Clinical Guideline CG58 (Prostate Cancer) was produced before degarelix
was available. Recommendations on the use of hormonal therapy are dependant
on the stage of the disease:
 Localised prostate cancer: adjuvant hormonal therapy for a minimum of 2
years in men receiving radical radiotherapy for localised prostate cancer
who have a Gleason score of ≥8 (high risk). Hormonal therapies are not
routinely recommended in men who have a biochemical relapse unless they
have symptomatic local progression or metastatic disease or a PSA
doubling time <3 months.
4.

Locally advanced prostate cancer: hormonal therapy is recommended as
neoadjuvant treatment for 3-6 months prior to radical radiotherapy and for 2
years afterwards in men with a Gleason score ≥8. It is not recommended in
addition to radical prostatectomy.

Metastatic prostate cancer: Hormonal therapy should be offered as an
alternative to bilateral orchidectomy. The treatments have been shown to
have similar efficacy. Orchidectomy is more cost effective but patient
preference may be an issue. Although there is no long term evidence of
effectiveness intermittent androgen blockade (using combined LHRH
analogue and anti-androgen) may also be offered.
Evidence of Clinical Effectiveness
4.1 Identification of key clinical trials
The Cochrane Clinical Trials database and PubMed were searched for relevant
studies. A PubMed search was conducted using the terms ‘degarelix’, ‘prostate
cancer’, ‘advanced prostate cancer’, ‘hormonal treatment’. This was supplemented
with additional searches to obtain specific parameter estimates for the economic
model. Table 1 lists the relevant studies of degarelix identified.
Table 1: Summary of Degarelix studies
Source
Klotz 2008
Gittleman 2008
Van Poppel 2008
Tombal 2009
Schroder 2009
Purpose of study
Phase III open label – efficacy and safety
Phase II dose finding study
Phase II dose finding
Sub-analysis of Klotz trial
Sub-analysis of Klotz trial
Additional data for the health economic model has been extracted from published
papers.
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4.2 Overview of clinical evidence
Non inferiority to leuprorelin in achieving castrate levels of testosterone from day 28
to day 364 has been demonstrated in a 1-year, open label, randomised controlled
trial of 610 men with prostate cancer (Klotz, 2008). This trial compared leuprorelin
7.5mg monthly, twice its UK licensed dose, with two different dose regimens of
degarelix; one arm was the licensed regimen, the other used twice the maintenance
dose. The proportion of responders was very similar between the treatments and
also across the different doses of degarelix studied. Degarelix achieved a more
rapid reduction in PSA levels than leuprorelin monotherapy (64% reduction at day
14 with degarelix compared to 18% reduction with leuprorelin). However, in patients
who received leuprorelin with concomitant bicalutamide, which could be prescribed
as flare cover at the investigators discretion, the PSA reduction was similar to that
achieved with degarelix. A testosterone surge was observed in 80% of patients on
leuprorelin compared to one on degarelix in the non-licensed dose group. There
was no difference in the rate of PSA failure (defined as an increase of 50% from
nadir and ≥ 5ng/ml) between any of the groups.
The higher rate of testosterone surge in the leuprorelin group is pharmacologically
predictable but only 11% of patients were prescribed anti-androgen cover. It is not
clear what the impact of the high dose of leuprorelin used is, either on efficacy or
adverse event profile.
Schroder (2009) reports changes in alkaline phopsphatase levels, a non-specific
biochemical marker of bone turnover, which were observed to be suppressed to
lower levels with degarelix than with leuprorelin. It is unclear what the clinical effects
of this are: the authors suggest that degarelix might offer better control of serum
alkaline phosphatase and might prolong control of skeletal metastases compared to
LHRHa over a 1-year treatment period.
Sub analysis reported by Tombal (2009) found lower incidence of PSA failure and
death in patients given degarelix compared to leuprorelin. However, there are a
number of limitations that require consideration. Firstly, these are exploratory
analyses involving a small number of events. Secondly, the risk of disease
progression is associated with baseline parameters which were not stratified at
baseline. PSA recurrence was experienced by the same proportion of patients in
the leuprorelin and high-dose degarelix groups which both had more patients with
metastatic disease compared to the licensed-dose degarelix group. More patients
in the leuprorelin and high dose degarelix groups had metastatic disease at
baseline and PSA recurrence was experienced by the same proportion of patients
in each group. Furthermore, the median age of patients in the leuprorelin group was
2 years older than the degarelix groups. The median age in the two degarelix
groups was the same as was the number of deaths. It is thus not clear if the
probability of death is related to a treatment effect or the age of the patients. Fewer
patients in the licensed-dose degarelix group were also in the highest group of
baseline PSA (>50ng/ml). There was no difference in risk of PSA recurrence or
death in analyses that adjusted for baseline disease stage or PSA level.
4.3 Conclusions on clinical evidence
Data are limited to one year of follow up of surrogate biochemical markers. The
biochemical response in terms of testosterone suppression has been shown to be
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non inferior to leuprorelin. Survival has not been adequately assessed as a planned
outcome measure in a clinical trial.
Clinical opinion is that the principal benefit of degarelix would be the absence of
testosterone flare. Secondary endpoint data support that degarelix is not associated
with this effect. The clinical benefit of this is dependant on the circumstances in
which degarelix would be used. Avoidance of spinal cord compression
complications and bladder outlet obstruction are those of most clinical interest. We
could find no trial work that examined comparative rates of these events. A high
rate of biochemical testosterone flare was observed in the leuprorelin group in
which only a minority of patients were given prophylactic androgen cover for any
adverse events this might be associated with. This is in contrast to routine clinical
practice when initiating LHRHa in patients with metastatic disease. Despite this, no
serious adverse events associated with testosterone flare were reported in the trial.
5.
Discussion of evidence on safety
In the major comparative study of degarelix and leuprorelin there were a similar
proportion of treatment emergent adverse events in the 3 groups. The most
common were pharmacological predictable effects such as hot flushes (26%) and
weight gain (7%). Drug related adverse events were more common in the degarelix
groups, principally due to a higher incidence of injection site reactions (40% vs 1
patient with leuprorelin). Excluding injection site reactions, the incidence of adverse
events was similar for degarelix and leuprorelin. There were no reported instances
of the serious consequences of testosterone flare that are the subject of this
assessment in any of the treatment arms.
The SPC lists hot flushes and injection site reactions as very common adverse
events, with anaemia, weight increase, insomnia, dizziness, headache, diarrhoea,
nausea, hyperhidrosis, musculoskeletal pain, gynaecomastia and fatigue as
common adverse events. Many of these are expected due to testosterone
suppression.
6.
Summary of the clinical case
The clinical case is considered to be: equivocal.
Appendix 1 shows the criteria used to define the clinical case.
In summary, data are available assessing surrogate outcomes only.
The
attainment of castrate levels of testosterone is accepted as a useful surrogate to
assess efficacy in achieving control of hormone dependent disease. Degarelix
achieves this a few weeks sooner than occurs with LHRHa and maintains similar
levels over at least 1 year. No evidence was found that readily provided
characterisation of biochemical measures and clinical events related to testosterone
flare. The clinical benefit of avoidance of tumour flare with degarelix has not been
assessed in clinical trials as an outcome measure.
7.
Cost Effectiveness
In 2009 the manufacturer made submissions to the SMC (2009) and the All Wales
Medicines Strategy Group (2009). In both cases these included a cost-utility model
for the use of degarelix in place of goserelin plus anti-androgen flare cover in
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patients with metastatic disease. The manufacturer’s model used a three state
Markov model to follow patients over a lifetime horizon (calculated at 80 months) to
reflect expected average survival. The SMC noted a number of weaknesses in the
economic analysis including the use of a post hoc sub group analysis indicating a
non-significant difference in PSA failure rate, which could be accounted for by an
imbalance at baseline, and a different clinical reaction to PSA failure from current
practice.
A resubmitted model was subsequently accepted by the SMC (2011). This used
secondary endpoint data of PSA recurrence taken from the results of the one-year
randomised trial and interim results from an extension phase. These data were
extrapolated over a 20 year horizon by fitting a Weibull curve. In this model, those
treated with degarelix progressed to more expensive treatments due to PSA failure
at a slower rate than those treated with goserelin. This resulted in the increased
acquisition costs associated with degarelix being offset by reduced subsequent
treatment costs. Patients treated with degarelix were estimated to gain an extra
0.46 QALYs. The clinical data used in this model is derived from a post hoc sub
group analysis which found a difference between degarelix and leuprorelin of
borderline significance with wide confidence intervals and based upon low
numbers. There is thus considerable uncertainty about the difference in clinical
progression between degarelix and leuprorelin treated patients.
The model assumes that goserelin has an equivalent effect to the leuprorelin used
in the clinical trial of degarelix. Whilst the assumption of an equivalent effect of the
different LHRHa may not be unreasonable, cheaper LHRHa therapy with triptorelin
is available on the NHS which could have been used in the model. In the South
West Peninsula, triptorelin has been adopted for several years as an alternative
LHRHa to goserelin and is over £200 per year cheaper than goserelin. Additionally,
the key clinical advantage noted by the EMEA (2008) and echoed by clinical
opinion is the avoidance of initial testosterone surge which has been proven in the
clinical study, whilst there are no conclusive data on clinical progression.
Our economic evaluation, (Lu et al., 2011) considers whether using degarelix to
achieve castrate levels of testosterone whilst avoiding the testosterone flare is cost
effective compared to using triptorelin with anti-androgen cover. Our evaluation
consists of a decision tree and a Markov submodel to estimate the cost
effectiveness of degarelix compared to triptorelin plus short term anti-androgen
cover in the management of patients with metastatic prostate cancer. The model
takes an NHS perspective and incorporates health state utilities and costs
associated with time spent receiving treatment for clinical symptoms due to initial
flare, time spent receiving hormonal treatments, response, progressive disease and
death. Costs and benefits were discounted at 3.5%.
It was the opinion of local clinicians that the main difference in effectiveness
between degarelix and triptorelin was the initial flare caused by triptorelin that may
lead to two major complications, spinal cord compression (SCC) and bladder outlet
obstruction (BOO). These events are poor clinical outcomes for patients and result
in additional NHS expenditure.
To capture the differences in costs and utilities due to these significant events
within the first month of the two hormonal treatments, the model consisted of a
decision tree for these short-term events. The effectiveness of the two treatments
after the initial month is assumed to be the same, i.e. progression-free survival and
long term survival for both treatments are assumed to be the same. A Markov
submodel was used to follow patients from the end of the first month to death. The
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time horizon of the model is 10 years after which time 96% of the patients are
expected to have died.
Sensitivity analyses were conducted to assess the effect of uncertainty around the
model structure and the impact of variation in certain key parameters that were
expected to have a strong influence of the cost effectiveness analysis. Such
analyses included a variation in price of degarelix and the proportion of SCC and
BOO events due to initial flare when patients are treated with triptorelin.
The price of degarelix used was £305.50 for the first 240mg dose, reflective of list
price plus VAT payable on hospital initiated treatment and £129.37 for the 80mg
maintenance injection, the list price excluding VAT as it is assumed that treatment
would continue in the community. The manufacturer offers individual PCTs a
rebate scheme but the details are commercial in confidence. A sensitivity analysis
was undertaken to examine the effect of the uncertainty in the data.
Our analysis will help commissioning groups decide upon the acceptability of any
rebate scheme they are offered.
Results
 In the base case scenario, the ICER for degarelix compared to triptorelin
plus anti androgen was £59,000 per QALY gained.
8.

The model suggests that the biggest sources of variation to the cost
effectiveness case are the price of degarelix, the rate of progression of the
disease, the proportion of patients who suffer spinal cord compression on
initiation of LHRH therapy, and the proportion of cases of SCC that are
severe. Of these sources of variation the most robustly characterised
parameter is the price of degarelix.

The ICER was very sensitive to the price of degarelix. If the price was 70%
of the market price, degarelix dominated, ie it costs less and produces more
QALYs compared with triptorelin plus anti-androgen.
Summary of the cost-effectiveness case
The cost effectiveness case is: restricted cost effectiveness.
Appendix 1 shows the criteria used to define the cost-effectiveness case.
Our analysis estimates an ICER of £59,000/QALY for degarelix at list price
compared to treatment with triptorelin plus short term anti androgen. There is
considerable uncertainty in this finding due largely to uncertainty in the rate of
serious complications of flare. Using the upper and lower bounds of the confidence
intervals from the largest available data set of serious short term complications the
cost/QALY varies from £28,000-£124,000. At a discount of 30% to the list price, the
cost effectiveness of degarelix dominates, i.e. it achieves greater benefits at less
cost than the comparator.
9.
Budget Impact
It was estimated that 106 patients across the South West Peninsula population of
1.6 million would be considered for treatment with degarelix. This gives an
estimated additional drug acquisition cost of £79,076 expected in the first year. This
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will be partially offset by a reduction of costs associated with spinal cord
compression (1 case) and bladder outlet obstruction (up to 9 cases). If the patient
cohort remains on treatment past 1-year, an additional drug acquisition cost of
£76,744 is incurred with no expected offset costs from reduced clinical events.
The above costs may be reduced if a PCT chooses to access a rebate scheme
offered by the manufacturer. The net budget impact may then be cost saving.
10.
Authors
This HTA has been produced by the Peninsula Health Technology Operations
Group. Clinical aspects of treatment of metastatic prostate cancer have been
discussed with local specialists. Support for the cost effectiveness analysis has
been provided by PenCLAHRC at the Peninsula College of Medicine and Dentistry
through work partially funded by the National Institute of Health Research (NIHR).
This collaboration gives access to an expert resource with experience of producing
appraisals for NICE. The authors have no interests to declare.
11.
Update September 2011
The full details of the cost effectiveness evaluation have been published.
Lu L., Peters J., Roome C., Stein K. (2011) Cost effectiveness analysis of degarelix
for advanced hormone-dependent prostate cancer. BJU Int Article first published
online: 23 AUG 2011 DOI: 10.1111/j.1464-410X.2011.10434.x
The Peninsula Health Technology Commissioning Group considered the
implications of the SMC decision to accept the revised health economic model
supporting the use of degarelix in Scotland. It was considered that the revised
economic analysis would not alter the decision of the Peninsula Health Technology
Commissioning Group. This was because of uncertainty in the robustness of data
on disease progression, the use of goserelin as the comparator in the model, and
that the principal potential advantage of degarelix as identified by the EMEA and
echoed by clinical opinion was the avoidance of testosterone surge, which was not
included in the model.
11
12. References
All Wales Medicines Strategy Group (2009) Degarelix (Firmagon) for the treatment
of advanced hormone-dependent prostate cancer. Advice No. 2109.
EMEA (2008) Assessment report for Firmagon. European Medicines Agency Doc
Ref EMEA/CHMP?635761/2008
Gittlema M et al. (2008) A 1-year, open label, randomized phase II dose finding
study of degarelix for the treatment of prostate cancer in North America. J Urol,180:
1986-92
Klotz L et al. (2008)The efficacy and safety of degarelix: a 12-month, comparative,
randomized, open-label, parallel-group phase III study in patients with prostate
cancer. BJU Int 102: 1531-8
NICE. (2008) Prostate Cancer CG 58: diagnosis and treatment. February 2008
Summary of Product Characteristics.
September 2009.
Degarelix.
Ferring Pharmaceuticals Ltd.
Scottish Medicines Consortium (2009) Degarelix 120mg and 80mg powder and
solvent for solution for injection (Firmagon). Drug Advice No 560/09.
Scottish Medicines Consortium (2011) Degarelix 120mg and 80mg powder and
solvent for solution for injection (Firmagon). Drug Advice No 560/09 resubmission.
Tornoe C et al. (2007) Population pharmacokinetic/pharmacodynamic (PK/PD)
modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH
analogues. Br J Clin Pharmacol 2007;63: 648-64
Van Poppel H et al.(2008) Degarelix: a novel gonadotropin-releasing hormone
(GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2
dosage-finding study in the treatment of prostate cancer. Eur Urol 54, 805-13
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Appendix One: Peninsula Health Technology Commissioning Group
Criteria used to define the clinical and cost-effectiveness case
1.
Clinical case
Category
Generally Supportable
Supportable with
restrictions
Equivocal
Not supportable
2.
Criteria
There is robust, preferably reproduced, evidence of a benefit likely to be
considered meaningful by patients and which is likely to be applicable to
the majority of the patients. The clinical case would support
commissioning.
There is evidence of a benefit likely to be considered meaningful by
patients with the condition to be treated but it is likely to be limited only
to certain subgroups (which the Task Specific Group should define).
Commissioning for use in the defined subgroup would be appropriate.
There are data suggestive of a benefit but this is derived from studies
which are not conclusive or where data are conflicting. Examples may
also include
 The benefit may only be apparent in certain subgroups of
patients which are not readily defined.
 Professional bodies may recommend treatment but this is
based upon consensus rather than trial evidence of the direct
benefit of the technology in the condition under consideration

Data are available demonstrating evidence only of
improvements in surrogate outcomes which may not translate
into objective benefits likely to be considered meaningful by
patients.
There are significant difficulties and limitations to the data. Examples
may include: Significantly different patient populations studied to that
treated locally, significant doubts about the robustness of trial data.
Cost effectiveness case
Category
Generally cost effective
Restricted cost
effectiveness
Not cost effective
Criteria
Cost effectiveness considerations suggest that under general use the
technology compares favourably with other interventions that have been
assessed nationally as a cost effective use of NHS resources.
Cost effectiveness considerations suggest that the technology only
compares favourably with other nationally assessed cost effective
technologies under restricted circumstances. The task specific group
should describe these circumstances. Such circumstances may include
identifiable sub groups, or assumptions about outcomes that have not
been proven.
Cost effectiveness considerations suggest that the technology is likely
to have similar cost effectiveness to interventions that have been
assessed nationally as not cost effective.
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