Degarelix (Firmagon) induction and maintenance for advanced hormone-dependent prostate cancer

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1 LONDON CANCER NEW DRUGS GROUP RAPID REVIEW Degarelix (Firmagon) induction and maintenance for advanced hormone-dependent prostate cancer Degarelix (Firmagon) induction and maintenance for advanced hormone-dependent prostate cancer December 2012 (partial revision October 2013) Contents Background 2 Epidemiology 3 Guidelines 3 Published data 3 Cost-effectiveness 6 Audit 7 Costs 7 Points for consideration 8 References 8 Produced for the London New Drugs Group Contact: Yuet Wan Medicines Information Pharmacist London & South East Medicines Information Service Guy s Hospital London SE1 9RT Tel: Fax: Yuet.wan@gstt.nhs.uk Further copies of this document are available from URL NeLM-Area/Evidence/Drug- Specific-Reviews/ Produced for use within the NHS. Not to be reproduced for com- Summary Information in this review has been taken largely from the AWMSG appraisal In contrast to the luteinising hormone-releasing hormone (LHRH) agonists, degarelix (Firmagon) is a LHRH antagonist that directly blocks the GnRH receptors, and is licensed for the treatment of patients with advanced hormone-dependent prostate cancer. The starting dose is 240 mg administered as two subcutaneous injections of 120 mg each, followed a month later by maintenance doses of 80mg every month. The pivotal phase III study of degarelix (CS21) in 610 patients reported non-inferiority to leuprorelin at maintaining low testosterone levels (suppression to 0.5 ng/ml at all monthly measurements) over a 1- year treatment period [97.2% degarelix 80mg group vs. 96.4% leuprorelin 7.5mg group] and faster testosterone and PSA suppression with degarelix, though beyond 28 days, there was no significant difference in the degree of testosterone suppression. In addition, degarelix did not induce testosterone surge or microsurges, however, anti-androgen treatment was administered to only 11% of patients receiving leuprorelin, and in this subgroup, the incidence of testosterone surge during the first two weeks of treatment was lower than in patients receiving leuprorelin only, thus it remains unclear whether degarelix offers any clinical benefit in terms of avoidance of testosterone flare over an LHRH agonist, used in combination with an antiandrogen. Degarelix treatment was associated with higher incidences of injection site reaction (35% vs. <1% leuprorelin group), which occurred predominantly after the first injection. The most frequently reported adverse event was flushing (26% degarelix vs. 21% leuprorelin). In addition, more degarelix-treated patients reported chills (3% vs. none), while more patients in the leuprorelin group reported arthralgia (5% versus 9%) and urinary tract infections (5% vs. 9%) Patients who completed the study were eligible to enter the extension study (CS21A), and either continued on same monthly degarelix maintenance dose or were re-randomised from leuprorelin to degarelix. At median follow-up of 27.5 months, similar proportions of patients in the degarelix and leuprorelin groups discontinued due to adverse events [10% and 16%, respectively] and 6 per group died during treatment. Testosterone and PSA remained suppressed in patients on degarelix and in those who switched to degarelix. Up to 1 year, the risk of PSA failure or death was lower in patients on degarelix; and beyond 1 year, this risk decreased in patients who switched from leuprorelin to degarelix. The PSA PFS hazard rate had decreased from 0.20 events annually in year 1 to 0.08 events annually after the switch in the leuprorelin/degarelix group (p=0.003).

2 A 12 week phase III study in 182 patients comparing degarelix (240 mg and monthly maintenance dose of 80 mg) with goserelin 3.6 mg monthly (with 50 mg bicalutamide daily for initial 28 days of treatment) reported a similar mean percentage change in total prostate volume ( 37.2% degarelix vs. 39.0% goserelin group) and met the predefined non-inferiority criterion. Treatment-emergent adverse event were reported by 39% and 48% of patients on degarelix and goserelin respectively, of which 2% and 11% were considered severe, while 35% in each group were considered treatmentrelated. Most adverse drug events were injection site reactions, (predominantly pain, 14%; erythema, 4%; swelling, 4%), which were reported by degarelix-treated patients only. It is noted that clinical improvement in terms of survival or tumour reduction has not been explored as part of a pre-defined endpoint in studies to date, the population for which degarelix is licensed (advanced prostate cancer) encompasses only 50% of the pivotal study population, and the dose of leuprorelin used in the pivotal study is higher than the dose licensed in the UK. In addition, degarelix is administered monthly by subcutaneous injection and requires reconstitution before injection, whereas the LHRH agonist comparators are available in formulations that can be administered less frequently (every 3 6 months) and do not require reconstitution. The AWMSG and the SMC support the use of degarelix as an option for the treatment of patients with advanced hormone-dependent prostate cancer provided the approved Patient Access Scheme is utilised. Guidance from NICE is expected in May According to guidelines from the European Association of Urology, the LHRH antagonists seem appealing, but their advantages over LHRH agonists are far from proven, and suppression of the initial flare-up with monotherapy is only clinically relevant in a few symptomatic metastatic patients The cost (full list price) of degarelix in the first year is 1683 then 1552 in subsequent years. The annual cost of LHRH agonists is in the range 900 to A patient access scheme (simple rebate scheme) has been reviewed and approved by LPP and is now available in London. Background Androgen deprivation (AD) is the mainstay of advanced prostate cancer management, which can be achieved through bilateral orchidectomy or by administration of long-acting luteinising hormone-releasing hormone (LHRH; also known as gonadotrophin-releasing hormone [GnRH]) agonists, such as goserelin, leuprorelin and triptorelin. These agents suppress testosterone production to castration levels (0.5 ng/ml) within 2 3 weeks of treatment initiation in % of patients. The initial physiological response to these agents results in a supraphysiological increase in testosterone levels, also known as a biochemical surge, which might stimulate prostate cancer cells and lead to an exacerbation of clinical symptoms such as spinal cord compression, bone pain and urethral obstruction (termed flare ). Antiandrogens can be administered to mitigate the symptoms of clinical flare. 1,2 The GnRH antagonist is a new class of agent that immediately blocks the GnRH receptor and thus produces rapid AD without the ensuing testosterone surge. One such agent is degarelix (Firmagon), which binds to and blocks the GnRH receptors in the anterior pituitary gland, resulting in decreased secretion of both luteinising hormone (LH) and follicle stimulating hormone (FSH). This leads directly to a rapid decrease in the production of testosterone, which reaches castrate levels within 1 3 days of administration. 1,2 Degarelix is licensed for the treatment of patients with advanced hormone-dependent prostate cancer. The starting dose is 240 mg administered as two subcutaneous injections of 120 mg each, followed a month later by maintenance doses of 80mg every month. 3

3 Epidemiology In 2009, there were 40,841 cases of prostate cancer diagnosed in the UK. The crude incidence rate indicates that there are around 135 cases for every 100,000 men. The latest estimates of prevalence for the UK show that around 181,000 men were still alive at the end of 2006, up to ten years after being diagnosed with prostate cancer. 4 Guidelines The AWMSG and the SMC support the use of degarelix as an option for use within NHS Wales and NHS Scotland, respectively, for the treatment of patients with advanced hormonedependent prostate cancer provided the approved Patient Access Scheme is utilised. 5,6 Guidance from NICE is expected in May According to guidelines from the European Association of Urology, the LHRH antagonists seem appealing, but their advantages over LHRH agonists are far from proven, and suppression of the initial flare-up with monotherapy is only clinically relevant in a few symptomatic metastatic patients. Further trials are needed to confirm the preliminary observed increased efficacy compared to leuprorelin. In addition, the use of LHRH antagonists is limited by a monthly formulation, compared with 3-month and 6-month depot formulations for the available LHRH analogues. 8 Published data Pivotal study: comparison of degarelix with leuprorelin (CS21) This randomised, open-label, 12-month, phase III study compared degarelix with leuprorelin for maintaining testosterone suppression in 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/ml, median prostate-specific antigen, PSA, level 19.0 ng/ml, ECOG 2 and life expectancy 12 months). The main exclusion criteria were any previous or current hormonal treatment for prostate cancer, apart from neoadjuvant/adjuvant therapy ( 6 months duration) that ended at least six months before study inclusion. Patients considered to be candidates for curative therapy were also excluded. 1,2 The participants were randomised (1:1:1) to one of three treatment arms: Initial subcutaneous degarelix injection 240 mg, followed by monthly maintenance dose of 80 mg As above, followed by monthly maintenance dose of 160 mg Leuprorelin 7.5 mg as a single monthly intramuscular injection (+/ - bicalutamide 50mg once daily, during treatment initiation to prevent clinical flare at discretion of the investigator). The primary endpoint was suppression of testosterone to 0.5 ng/ml at all monthly measurements from day 28 to day 364, thus defining the treatment response. The effectiveness of degarelix was determined by showing that: 1,2 (i) The lower limit of the 95% CI for the cumulative probability of testosterone being 0.5 ng/ ml from 28 to 364 days for degarelix was 90%. (ii) degarelix was not inferior to leuprorelin for the cumulative probability of testosterone levels being 0.5 ng/ml from 28 to 364 days. The non-inferiority margin for the difference between treatments (degarelix vs leuprorelin) was -10%. Secondary endpoints included the proportion of patients with testosterone surge during the first two weeks of treatment (testosterone levels exceeding baseline by 15% on any 2 days during the first two weeks of treatment), qualityof-life outcomes and percentage change in PSA from baseline to day 14 and day 28. Of the 201 patients in the leuprorelin group, 23 (11%) received concomitant bicalutamide for flare protection at the start of treatment. 2 Of these patients, 9 patients had metastatic disease and 14 had PSA >20 ng/ml at baseline. 9 Of the 178 patients in the leuprorelin group who did not receive bicalutamide, 144 (81%) had a surge in testosterone (testosterone increase of 15% from baseline, on any 2 days during the first 2 weeks).

4 Among the 40 patients in the leuprorelin group who did not fulfil the pre-set criteria for a testosterone surge, about half had one testosterone value of 15% from baseline during the first 2 weeks. None of the patients receiving degarelix had a testosterone surge. 1,2 As the licensed maintenance dose of degarelix is 80mg, results from this treatment group are reported here: 1,2 The primary endpoint (testosterone response rate) in the ITT population was achieved by 97.2% in the degarelix 80mg group and 96.4% in leuprorelin-treated patients; difference between treatment arms was 0.88% (97.5% CI: to 4.96), which fulfilled the pre-specified criterion for demonstration of non-inferiority of degarelix to leuprorelin (i.e. lower limit 97.5% CI > - 10%). At 3 days after starting treatment, testosterone levels were 0.5 ng/ml in 96.1% of patients in the degarelix group and in none of patients in the leuprorelin group. Reduction of PSA levels from baseline at day 14 and 28 was greater in degarelixtreated patients than the leuprorelin group; however, PSA level reduction in the small subgroup of patients receiving leuprorelin with bicalutamide (n = 23) were similar to those in degarelix-treated patients. Quality-of-life outcomes were comparable between the groups. An exploratory subgroup analyses was conducted of PSA data from the CS21 trial. PSA recurrence (secondary end point) was defined as two consecutive increases in PSA of 50% compared with nadir and 5ng/ml on two consecutive measurements at least 2 weeks apart. The following findings were noted: 9 PSA recurrence occurred more frequently in patients on leuprorelin (12.9%) compared with degarelix 240/80 mg (7.7%). The probability of completing the study without experiencing PSA recurrence by day 364 was 91.1% for degarelix and 85.9% for leuprorelin. The probability of completing the study without dying by day 364 was 97.4% for degarelix and 95.1% for leuprorelin. Patients receiving degarelix had a statistically lower risk of PSA recurrence or death compared with leuprorelin (p = 0.05) but adjusting for baseline disease stage and PSA resulted in a non-statistically significant difference (hazard ratio 0.664; 95% CI, ). PSA recurrence occurred more frequently in patients with advanced disease in both treatment groups: in patients with metastatic disease, 21.6% of those in the degarelix 240/80mg group and 36.2% in the leuprorelin group experienced PSA recurrence (p = 0.156). A similar proportion of degarelix patients experienced PSA recurrence in the locally advanced subgroup compared with leuprorelin. PSA recurrence was more frequent in patients with higher baseline PSA in both treatment groups. All recurrences occurred in those with baseline PSA>20ng/ml; for patients on degarelix with baseline PSA >20ng/ml, risk of PSA recurrence was statistically significantly lower (p=0.04) but in patients with baseline PSA >50ng/ml, 29.2% of those receiving degarelix and 40.0% of those receiving leuprorelin experienced PSA recurrence (p = 0.10) Extension study CS21A Patients who completed the phase III study (n= 504) were eligible to enter the extension study (CS21A), and 385 either continued on the same monthly degarelix maintenance dose (160 or 80 mg, n= 125 each group), or were rerandomised from leuprorelin 7.5 mg to degarelix 240/80 mg (n= 69) or 240/160 mg (n= 65). At randomisation primary data on CS21 had not been conclusively analysed and, thus, patients on leuprorelin were switched to either maintenance degarelix dose. Upon receiving regulatory approval of degarelix 240/80 mg, patients on the 160 mg dose were switched to the approved dose. CS21A was initiated in March 2007 and the database was analysed in March 2010 at a median follow-up of 27.5 months.

5 The primary objective of CS21A was to evaluate safety and tolerability during long-term degarelix treatment. Secondary objectives were to evaluate testosterone, PSA, LH and FSH responses, and PSA failure and progression-free survival in patients who continued on degarelix or switched from leuprorelin. PSA failure was defined as 2 consecutive PSA increases of 50% vs. nadir and 5 ng/ml on 2 consecutive measurements 2 or more weeks apart. Time to an event was defined as the number of days from dose 1 to the first of PSA failure or death. 10 Data are shown for the approved degarelix 240/80 mg dose group. Data on patients who switched from leuprorelin to degarelix 240/160 and 240/80 mg were pooled (leuprorelin/ degarelix group). At a median follow-up of 27.5 months: 51 patients on degarelix and 62 switched from leuprorelin had discontinued the study. Similar proportions of patients in the degarelix and leuprorelin groups discontinued due to adverse events (AEs) [10% and 16%, respectively] and 6 per group died during treatment. 74 and 72 patients in the degarelix and leuprorelin groups, respectively, continued in the study. Median testosterone remained suppressed at less than 0.2 ng/ml in patients on degarelix and in those who switched to degarelix from leuprorelin at all time points measured PSA remained suppressed (median less than 1 ng/ml) in each group Up to 1 year, the risk of PSA failure or death was lower in patients on degarelix vs. leuprorelin (p=0.05). Beyond 1 year, the risk of PSA failure or death decreased in patients who switched from leuprorelin to degarelix. The PSA PFS hazard rate had decreased from 0.20 events annually in year 1 to 0.08 events annually after the switch in the leuprorelin/degarelix group (p=0.003). The corresponding hazard rate in the continuous degarelix 240/80 mg group was 0.11 and 0.14 events annually (p =0.464), showing a consistent effect of degarelix with time. The same hazard rate change pattern occurred in the group with baseline PSA >20 ng/ml. The researchers conclude this extension trial suggests that effective suppression of testosterone and PSA can be maintained for greater than 3 years with degarelix 240/80mg, whilst in patients switched from leuprorelin to degarelix, testosterone and PSA suppression were also maintained at consistent levels after 1 year. 10 Comparison of degarelix with goserelin This 12 week randomised, open-label, phase III study in 182 prostate cancer patients compared degarelix (starting dose 240 mg and monthly maintenance dose of 80 mg) with goserelin 3.6 mg monthly (with 50 mg bicalutamide daily for initial 28 days of treatment). The primary efficacy endpoint was mean percentage change in total prostate volume which was similar between the treatment groups ( 37.2% degarelix group vs. 39.0% goserelin-treated patients) and met the predefined non-inferiority criterion. 1 Comparative safety In the CS21A study, the most frequently reported AE in the degarelix 240/80mg group was flushing (26% degarelix vs. 21% leuprorelin). 1 Degarelix was associated with a higher rate of injection-site reactions than leuprolide (35% vs <1%, P<0.001, respectively), which occurred predominantly after the first injection; 33% of 409 starting-dose injections and 4% of 2244 and 2208 maintenance-dose injections (240/80 and 240/160 mg groups, respectively) were reported to be associated with injectionsite reactions. 2 In addition, more degarelixtreated patients reported chills (3% vs. none), while more patients in the leuprorelin group reported arthralgia (5% versus 9%) and urinary tract infections (5% vs. 9%). Cardiovascular side effects were reported by 9% and 13% in patients receiving degarelix (combined 80 mg and 160 mg dose treatment groups) and leuprorelin, respectively. Discontinuations due to AEs occurred in 15 (7%) degarelix-treated patients and 12 (6%) in the leuprorelin group. 1 The overall incidence of treatment emergent AEs was similar in the 2 groups throughout the

6 4 study years and it decreased as the extension study progressed. By year 4 the incidence of individual AEs was low in each group with no major between group differences. Switching from leuprorelin to degarelix was accompanied by more injection site reactions in year 2, however, the incidence of these effects decreased in years 3 and 4 to attain similar levels in the 2 groups. 9 In the goserelin study, treatment-emergent AEs were reported by 39% and 48% of patients receiving degarelix and goserelin respectively, of which 2% and 11% were considered severe, while 35% in each group were considered treatment-related. Most AEs reported were injection site reactions, which were reported in the degarelix group; these were predominantly pain (14%), erythema (4%) and swelling (4%). 1 Cost-effectiveness 1 The company submission to the AWMSG describes a cost utility analysis of degarelix, administered once monthly, for the treatment of advanced hormone-dependent prostate cancer. The primary comparator considered is leuprorelin, administered at its licensed dose (11.25 mg once every three months), with bicalutamide 50 mg daily for four weeks, for testosterone surge protection. Alternative LHRH agonists are also considered as comparators (leuprorelin 3.75 mg monthly, and goserelin and triptorelin administered monthly or three-monthly at licensed doses). The analysis considers three states: prostate cancer first line treatment prostate cancer second line and subsequent line treatment death The model estimates first-line degarelix treatment to generate more quality-adjusted life-years (QALYs) at lower overall costs than the comparator in both the whole advanced hormone-dependent prostate cancer population and the subgroup with baseline PSA > 20 ng/ml. The results are driven by the modelled difference in PSA recurrence rates, which lead to patients on degarelix treatment remaining in the first-line treatment state, with the highest quality of life, for longer, and patients on leuprorelin treatment progressing more quickly onto more costly second- and subsequent-line treatments, with lower quality of life. A sensitivity analyses suggest the probability of degarelix being cost-effective is over 94% at a threshold of 20,000 per QALY gained, with the vast majority of simulations indicating dominance (i.e. costs less and produces more QALYs) over leuprorelin. It is not certain that the base case analyses provided by the company represent the most plausible estimates of the costeffectiveness of degarelix in practice. However, in extensive sensitivity and scenario analyses, many modelled estimates consistently fell within conventional thresholds for costeffectiveness, in the context of the price agreed with Patient Access Scheme. Two studies of the cost-effectiveness of degarelix within its current licensed indication have been published. The first study is an abstract/ poster presentation of the economic evidence resubmitted to the SMC by the company, which suggested that degarelix is dominant over goserelin. The second study is a published cost utility analysis of degarelix compared against triptorelin plus short-term anti-androgen treatment in the management of patients with metastatic prostate cancer, which was originally conducted to inform local decision-making in South-West England. The model consisted of a decision tree monitoring a hypothetical cohort of patients aged 70 years from the start of hormonal treatment to the end of the first month, and a Markov model monitoring patients from the end of month one for a time horizon of 10 years. In the base case analysis, the ICER for degarelix compared to triptorelin plus antiandrogen treatment was 59,000 per QALY gained. The ICER was very sensitive to the price of degarelix, and if the price was reduced to 70% of the market price, degarelix became dominant over triptorelin plus anti-androgen treatment. 1

7 Audit An audit on the safety profile, clinical and PSA response with use of degarelix was conducted in three hospitals in the North East of England. It involved 35 consecutive patients [mean age 70.9 years ( ) and mean PSA level at presentation 759 ng/ml] who commenced treatment between May 2010 and August 2011, of whom 82.9% had PSA >50ng/ml. A number of symptoms at diagnosis were also recorded, with 5 (14.2%) patients having acute urinary retention and 1 (2.8%) spinal cord compression. Bone pain was the most common symptom in 14 (39.9%) patients. The mean time from the first injection to the first PSA check was 5.8 weeks (range weeks). The mean time from first injection to achievement of PSA nadir was 14.4 weeks (range weeks). The mean follow-up was 37.1 weeks (range ). All 35 patients had an initial biochemical PSA response. PSA levels at the latest follow-up (from nadir) rose in 14 (40%) patients. The mean time for the rise of PSA from nadir was 27.5 weeks (range weeks). A total of 21 patients (60%) were currently on degarelix only and continued to respond to treatment. Of the 13 patients with bone pain, 3 (23%) reported a reduction in bone pain after treatment with only degarelix. One patient had an MI while receiving degarelix, although this patient did have a previous history of ischaemic heart disease. 11 Cost 1 Examples of annual costs for treatment of prostate cancer. Degarelix 80 mg and 120 mg vials LHRH agonists Leuprorelin (Prostap ) injection 3.75 mg vial Leuprorelin (Prostap ) injection mg vial Goserelin (Novgos ) implant 3.6 mg prefilled syringe Goserelin (Zoladex ) implant 3.6 mg in syringe applicator Goserelin (Zoladex LA) implant 10.8 mg in syringe applicator Triptorelin (Decapeptyl SR) Injection 3mg vial Triptorelin (Decapeptyl SR) Injection mg vial Example regimen Initially two 120 mg by subcutaneous injection, then 80 mg every month. One injection monthly 903 One injection every three months 903 One implant every 28 days 763 One implant every 28 days 848 One implant every 12 weeks 1,018 One injection every four weeks 897 One injection every three months 828 Triptorelin (Decapeptyl SR) One injection every six months 828 Injection 22.5 mg vial Triptorelin (Gonapeptyl Depot) One injection every four weeks 1, mg injection Gonadorelin analogues Histrelin (Vantas ) 50 mg implant One implant every 12 months 990 Buserelin (Superfact ) Injection 1 mg/ml Intranasal spray 100 microgram per metered spray 500 microgram injection every eight hours for seven days Then one intranasal spray into each nostril six times daily 1,116 Short-term anti-androgens for testosterone flare protection with LHRH agonists Bicalutamide (non-proprietary) tablets, 50 mg Cyproterone (non-proprietary) Tablets, 50 and 100 mg Flutamide (non-proprietary) tablets, 250 mg 50 mg once daily started at least three days before gonadorelin therapy 100 mg twice daily for 7 days before initiation of gonadorelin analogue, followed by 100 mg twice daily for 3 4 weeks Approximate annual cost 1,683 in first year 1,552 subsequent years (full list price)* mg three times daily 38 Cost of degarelix is based on the full list price. Other drug costs are based on BNF 63 and MIMS list prices as of 1 August This table does not imply therapeutic equivalence of the stated drugs and doses Cost based on a total course of four weeks

8 Patient access scheme Ferring Pharmaceuticals has an agreement in place with London Procurement Partnership to rebate a % of the cost of degarelix. This is a replication of the SMC & PASAG system in Scotland and the AWSMG & PASAW agreement for Wales. 12 Points for consideration The AWMSG noted that though the noninferiority of degarelix in comparison with leuprorelin and goserelin was demonstrated in terms of surrogate primary endpoints (testosterone suppression and reduction in total prostate volume), clinical improvement in terms of survival or tumour reduction has not been explored as part of a pre-defined endpoint. However, post-hoc analysis of progression-free and overall survival from study CS21/CS21A suggests that there could also be a beneficial effect with degarelix 1 though this requires confirmation in further studies. Secondary endpoint data from study CS21 indicate that degarelix is not associated with an initial surge in testosterone levels but it remains unclear whether degarelix offers any clinical benefit in terms of avoidance of testosterone flare over an LHRH agonist provided an anti-androgen is given concomitantly. 1 The company suggests that in emergency situations, waiting for the effect of the anti-androgen may not be desirable. It was also highlighted that the leuprorelin 7.5 mg dose administered during study CS21/CS21A is currently unlicensed in the UK and does not therefore reflect use in practice of the more commonly prescribed three-monthly goserelin injection. 1 Furthermore, the submitted clinical studies enrolled patients with prostate cancer, including localised and non-classifiable disease, whereas marketing authorisation was subsequently granted for use in patients with advanced prostate cancer which encompasses only 50% of the pivotal study population. Lastly degarelix is administered monthly by subcutaneous injection and requires reconstitution before injection whereas the LHRH agonist comparators are available in formulations that can be administered less frequently (every 3 6 months) and do not require reconstitution. 1 References 1. AWMSG secretariat assessment report (full submission). Advice No Degarelix (Firmagon) 80mg and 120mg injection (based on evidence submitted by Ferring Pharmaceuticals (UK) on 6 July 2012). awmsgonline/app/appraisalinfo/ Klotz L, Boccon-Gibod L, Shore ND et al. 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 2008; 102 (11): Ferring Pharmaceuticals Ltd: Firmagon 120mg Injection. SPC. Date of revision of text 25/07/ medicine/21701/spc 4. Cancer Research UK. Prostate cancer incidence statistics (section updated 01/05/12). cancerstats/types/prostate/incidence/ 5. AWMSG. Degarelix (Firmagon ) 80 mg and 120 mg subcutaneous injection Resubmission by: Ferring Pharmaceuticals (UK). Final Appraisal Recommendation (Advice No: 4112, November 2012): Documents/371/degarelix%20 (Firmagon)%20FAR.pdf 6. SMC. Degarelix (Firmagon). Advice issued 17 January SMC_Advice/ Advice/560_09_degarelix_Firmagon/ degarelix Firmagon_Resubmission 7. NICE. Prostate cancer (advanced, hormone dependent) - degarelix depot [ID590]. TAG/ Heidenreich A, Bastian PJ, Bellmunt J, et al. Guidelines on prostate cancer. European Association of Urology Prostate % 20Cancer_LR % 20March % 2013th% pdf

9 9. Tombal B, Miller K, Boccon-Gibod L et al. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprorelin in prostate cancer patients segmented by baseline characteristics. Eur Urol 2010; 57 (5): Crawford ED, Tombal B, Miller K, et al. A phase III extension trial with a 1-arm crossover from leuprorelin to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer. J Urol 2011; 186, Vasdev N, McClurey P, Gray D, et al. An Audit to Evaluate the Clinical Safety and PSA Response of Firmagon (Degarelix) in Patients with Advanced Metastatic Prostate Cancer. J Cancer Res Updates, 2013; 2: Ferring Pharmaceuticals. Personal communication. Details of search strategy: AWMSG/ SMC/NICE/ EMC/ Cochrane Library/ NeLM/ NHS Evidence Embase/Medline Search History: 1. EMBASE; exp DEGARELIX/; 241 results. 2. EMBASE; exp PROSTATE CANCER/; results. 3. EMBASE; 1 AND 2; 184 results. 4. EMBASE; 3 [Limit to: Human and English Language]; 141 results. 5. MEDLINE; DEGARELIX.ti,ab; 77 results. 6. MEDLINE; exp PROSTATIC NEOPLASMS/; results. 7. MEDLINE; 5 AND 6; 38 results. 8. MEDLINE; 7 [Limit to: English Language and Humans]; 36 results. 9. EMBASE,MEDLINE; Duplicate filtered: [3 [Limit to: Human and English Language]], [7 [Limit to: English Language and Humans]]; 177 results. The document reflects the views of LCNDG and may not reflect those of the reviewers Please direct any comments to Yuet Wan, London & South East Medicines Information Service, Guy s Hospital, Great Maze Pond, London SE1 9RT Tel: , Fax: , Yuet.wan@gstt.nhs.uk