A cost–utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom

Figures & data

Figure 1. Current treatment pathway for advanced (locally advanced or metastatic) hormone-dependent prostate cancer. This pathway is based on the information derived from the NICE clinical guideline on prostate cancer (CG58)1, the EAU guidelines on prostate cancer6, and expert opinion from UK clinicians [Personal Communication. UK Clinical Experts]. EAU, European Association of Urology; GnRH, gonadotropin-releasing hormone; LHRH, luteinising hormone-releasing hormone; NICE, National Institute for Health and Care Excellence.

Table 1. Key model parameters applied per cycle (28 days).

Parameter	First cycle	Subsequent cycle	Source
Costs
Drug costs
Degarelix (list price)	£260.00	£129.37	BNF 6341
Goserelin–3 monthly	£82.72	£78.33
Goserelin–monthly	£69.39	£65.00
Leuprorelin–monthly	£79.63	£75.24
Leuprorelin–3 monthly	£79.47	£75.08
Triptorelin–monthly	£73.39	£69.00
Triptorelin–3 monthly	£73.39	£69.00
Anti-androgen addition (bicalutamide)	£9.73	£9.73
Anti-androgen substitution (cyproterone acetate)	£37.65	£37.65
Diethylstilbestrol (non-prop)	£109.86	£109.86
Docetaxel*	£9215.13
Abiraterone	£2737.09	£2737.09
Palliative care	£345.78	£345.78	Guest et al.42 inflated to 2011 prices43
Administration costs
First-line
Degarelix	£338.04	£26.00	PSSRU 201143, NHS reference
Goserelin–3 monthly	£338.04	£8.67	costs 2010–201144
Goserelin–monthly	£338.04	£26.00
Leuprorelin–monthly	£338.04	£26.00
Leuprorelin–3 monthly	£338.04	£8.67
Triptorelin–monthly	£338.04	£26.00
Triptorelin–3 monthly	£338.04	£8.67
Anti-androgen addition, substitution, withdrawal and diethylstibestrol
Degarelix	£338.04	£26.00
3-monthly comparators	£338.04	£8.67
Monthly comparators	£338.04	£26.00
Docetaxel*	£5029.25
Abiraterone	£693.20	£693.20
Efficacy–PSA progression
ITT hazard ratio for degarelix compared to LHRH agonists	1.71		CS21 trial12
PSA > 20 ng/mL hazard ratio for degarelix compared to LHRH agonists	1.74
Proportion with continued response–Anti-androgen addition	85%		EAU Guidelines6
Proportion with continued response–Anti-androgen substitution	85%
Proportion with continued response–Anti-androgen withdrawal	85%
Proportion with continued response–Diethylstilbestrol	88%
Proportion with continued response–Docetaxel	92%
Proportion with continued response–Abiraterone	86%		Abiraterone NICE HTA38
Utilities
First-line hormonal therapy	0.90		Bayoumi et al.40
Second-line hormonal therapy	0.80
Chemotherapy (docetaxel and abiraterone)	0.69		AWMSG Assessment Report for abiraterone39
Palliative care	0.40		Bayoumi et al.40
Annual discount rates
Discount rate–costs	3.5%		NICE Guidelines for health technology appraisal28
Discount rate–QALYs	3.5%

*Included as a lump sum cost based upon an average of 7.3 cycles of chemotherapy4. AWMSG, All Wales Medicines Strategy Group; BNF, British National Formulary; EAU, European Association of Urology; HTA, health technology assessment; ITT, intention to treat; LHRH, luteinizing hormone-releasing hormone; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; PSA, prostate-specific antigen; PSSRU, Personal Social Services Research Unit; QALYs, quality-adjusted life years.

Figure 2. Health states included in the model. In the base-case model, anti-androgen substitution and diethylstilbestrol are not included in the treatment pathway, and patients skip over these to the next state.

Figure 3. Log-normal curve fits to Kaplan–Meier data for (a) ITT and (b) PSA > 20 ng/mL populations. ITT, intention to treat; PSA, prostate-specific antigen.

Table 2. Scenarios modeled in sensitivity analyses.

Number	Scenario description	Base-case scenario	Alternative scenarios modeled
1	Benefit from reduction of adverse events related to clinical flare only	MSEs and SCC excluded, differential PSA progression rates included	MSEs and SCC included, PSA progression assumed equal
2	Extrapolation of PSA progression data	PSA progression modeled using fitted parametric curves	PSA progression assumed equal after 1 year
3	Choice of parametric curve for PSA progression rate	Log-normal	Weibull, log-logistic, exponential, Gompertz
4	Time horizon	30 years	5 years
5	Comparator	3-monthly leuprorelin	3-monthly triptorelin*
6	Inclusion of abiraterone	Abiraterone included	Abiraterone excluded
7	Increased utility weight for patients on palliative care	0.4	0.69
8	Increased response rates for second-line treatments	85–92%	95%
9	Degarelix at list price	Degarelix at PAS price	Degarelix at list price
10	Inclusion of anti-androgen substitution and diethylstilbestrol	Anti-androgen substitution and diethylstilbestrol not included	Inclusion of anti-androgen substitution and diethylstilbestrol

MSE, musculoskeletal event; PAS, patient access scheme; PSA, prostate-specific antigen; SCC, spinal cord compression.

*Triptorelin is the cheapest 3-monthly treatment and was also the comparator reported in Lu et al.17

Table 3. Results of the base-case model.

	Costs	QALYs	Incremental costs	Incremental QALYs	ICER
Deterministic results
ITT
Leuprorelin 11.25 mg	£22,922	3.58
Degarelix	£19,289	3.79	−£3633	0.20	Dominant
PSA > 20 ng/mL
Leuprorelin 11.25 mg	£28,751	3.33
Degarelix	£24,441	3.57	−£4310	0.24	Dominant
Probabilistic results
ITT
Leuprorelin 11.25 mg	£23,886	3.56
Degarelix	£19,306	3.80	−£4580	0.24	Dominant
PSA > 20 ng/mL
Leuprorelin 11.25 mg	£29,424	3.29
Degarelix	£24,459	3.57	−£4965	0.28	Dominant

ICER, incremental cost-effectiveness ratio; ITT, intention to treat: PSA, prostate-specific antigen; QALYs, quality-adjusted life years.

Table 4. Results breakdown.

	ITT population			PSA > 20 ng/mL population
Cost component	Degarelix	Leuprorelin	Difference	Degarelix	Leuprorelin	Difference
Drug cost–first-line hormonal treatment	£3904	£2616	£1288	£3132	£1875	£1257
Drug cost–second-line hormonal treatments	£224	£282	−£58	£320	£373	−£52
Drug cost–non-hormonal treatment	£8431	£11,833	−£3402	£11,974	£15,562	−£3587
Cost of staff time and tests–first-line hormonal treatment	£1424	£627	£797	£1198	£541	£657
Cost of staff time and tests–second-line hormonal treatment	£338	£387	−£50	£482	£511	−£29
Cost of staff time and tests–non-hormonal treatment	£1785	£2525	−£739	£2559	£3354	−£794
Cost of palliative care	£3183	£4652	−£1470	£4775	£6536	−£1761
Cost of adverse events	£0	£0	£0	£0	£0	£0
Total cost	£19,289	£22,922	−£3633	£24,441	£28,751	−£4310
QALYs–first-line hormonal treatment	2.96	2.40	0.56	2.36	1.72	0.64
QALYs–second-line hormonal treatments	0.27	0.38	−0.11	0.38	0.50	−0.12
QALYs–non-hormonal treatment	0.56	0.81	−0.25	0.83	1.11	−0.28
Total QALYs	3.79	3.58	0.20	3.57	3.33	0.24

ITT, intention to treat: PSA, prostate-specific antigen; QALYs, quality-adjusted life years.

Figure 4. Tornado diagrams of 10 most influential parameters for the (a) ITT and (b) PSA > 20 ng/mL populations. The impact of the efficacy hazard ratios is not included here. The sensitivity to these parameters is examined separately in threshold analyses. GP, general practitioner; ICER, incremental cost-effectiveness ratio; ITT, intention to treat; QALYs, quality-adjusted life years; PSA, prostate-specific antigen; WTP, willingness to pay.

Figure 5. Cost-effectiveness plane for (a) ITT and (b) PSA > 20 ng/mL populations. ITT, intention to treat; PSA, prostate-specific antigen; QALYs, quality-adjusted life years.

Table 5. Hazard ratio threshold analysis results.

	ITT population		PSA > 20 ng/mL population
WTP threshold	Parameter value	Percentage of the mean estimate of the hazard ratio (1.71)	Parameter value	Percentage of the mean estimate of the hazard ratio (1.74)
£30,000 per QALY	1.08	63%	1.06	61%
£20,000 per QALY	1.10	64%	1.07	61%
£0 per QALY	1.18	69%	1.13	65%

ITT, intention to treat; PSA, prostate-specific antigen; QALY, quality-adjusted life year; WTP, willingness to pay.

Figure 6. Return on investment threshold analysis. ITT, intention to treat; PSA, prostate-specific antigen.

Table 6. Scenario analysis results.

		ITT population			PSA > 20 ng/mL population
Scenario	Description	Inc. costs	Inc. QALYs	ICER	Inc. costs	Inc. QALYs	ICER
	Base-case results	−£3633	0.20	Dominant	−£4310	0.24	Dominant
1	MSEs and SCC included, PSA progression assumed equal	−£27	0.03	Dominant	−£246	0.03	Dominant
2	PSA progression assumed equal after 1 year	−£10	0.07	Dominant	−£895	0.11	Dominant
3	Weibull	−£3439	0.20	Dominant	−£4002	0.24	Dominant
	Log-logistic	−£3598	0.20	Dominant	−£4280	0.24	Dominant
	Exponential	−£3556	0.20	Dominant	−£4124	0.24	Dominant
	Gompertz	−£3639	0.21	Dominant	−£4445	0.25	Dominant
4	5-year time horizon	−£2716	0.10	Dominant	−£3993	0.14	Dominant
5	Comparator 3-monthly triptorelin	−£3422	0.20	Dominant	−£4158	0.24	Dominant
6	Abiraterone excluded	−£1582	0.22	Dominant	−£2196	0.26	Dominant
7	Palliative care utility weight 0.69	−£3633	0.11	Dominant	−£4310	0.13	Dominant
8	Response rates for second-line treatments 95%	−£3394	0.11	Dominant	−£4141	0.14	Dominant
9	Degarelix at list price	Confidential	0.20	Dominant	Confidential	0.24	Dominant
10	Inclusion of anti-androgen substitution and diethylstilbestrol	−£2616	0.16	Dominant	−£3269	0.19	Dominant
11	Inclusion of differential mortality	−£2533	0.26	Dominant	−£2726	0.31	Dominant

ICER, incremental cost-effectiveness ratio; Inc, incremental; ITT, intention to treat; MSE, musculoskeletal event: PSA, prostate-specific antigen: QALYs, quality-adjusted life years; SCC, spinal cord compression.

Table 7. Comparison to economic model reported by Lu et al.17.

	Model submitted to AWMSG	Model reported by Lu et al.17
Population	Advanced prostate cancer and a high-risk sub-population (PSA > 20 ng/mL)	Asymptomatic metastatic prostate cancer
Comparator	Leuprorelin	Triptorelin
Key modeled outcomes	Slowing progression to second-line treatments	Suppression of adverse events associated with testosterone flares
Cost sources	Drug costs from BNF 6341. Administration costs from Unit Costs of Health and Social Care 201143. Resource use costs from NHS reference costs 2010–201144, Guest et al.42 (inflated to 2011 prices)	Drug costs from BNF 5946, but with incorrect price of degarelix used. Administration costs from Unit Costs of Health and Social Care 200847. Resource use costs from NICE guidelines for SCC48, which uses NHS reference costs 2006–2007 and NHS reference costs 2009.
Utility values source	Bayoumi et al.40	Bayoumi et al.40, Bennett et al.49 and Hollingworth et al.50

AWMSG, All Wales Medicines Strategy Group; BNF, British National Formulary; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; PSA, prostate-specific antigen; SCC, spinal cord compression.

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