Preliminary Cost-Effectiveness and Cost-Utility Analysis of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma in Italy

Figures & data

Figure 1 Structure of the partitioned survival model.

Abbreviations: OS, overall survival; PFS, progression-free survival.

Table 1 Utilities and Disutilities Incorporated in the Model

	Value	Source
Utilities for health state
Pre-progression	0.869	EMPOWER-CSCC 1, Longworth et al^Citation29, Scalone et al^Citation30
Post-progression	0.846
Disutilities for AEs
Asthenia	0.073	Nafees et al^Citation32
Hypokalemia	0.090	Nafees et al^Citation32
Stomatitis or oral mucositis	0.151	Lloyd et al^Citation33
Neutropenia	0.090	Nafees et al^Citation32
Anemia	0.073	Nafees et al^Citation32
Thrombocytopenia	0.108	Tolley et al^Citation34
Febrile neutropenia	0.090	Nafees et al^Citation32

Table 2 Drug Costs Considered in the Model

	Posology	Acquisition Costs (€)	Administration Costs (€)	Sources
Cemiplimab	350 mg IV every 3 weeks up to 22 months	6,294.94 per 350 mg vial	37.1	GU n.134/2020,^Citation20 DRG 410^Citation35
Chemotherapy	100 mg/m^2 IV cisplatin every 3 weeks (up to 6 cycles)	371		DRG 410^Citation35

Table 3 Resource Use and Unit Costs in Pre-Progression, Post-Progression and End-of-Life Health States

Resource	Frequency	Proportion of Patients (%)	Unit Costs (€)	Source
Pre-progression
Surgery	One time	15	1,895	DRG 272–273^Citation35
Oncologist visit	2 per month	100	20.66	General visit (89.7)^Citation35
GP visit	1 per month	100	20.66	General visit (89.7)^Citation35
Blood test	2 per month	100	5.75	Venous blood sampling (91.49.2)^Citation35 + blood count (90.62.2)^Citation35
Palliative RT	0.33 per month	45	987.75	Stereotactic radiotherapy (92.24.4)^Citation35
Complex palliative RT	0.33 per month	30	987.75	Stereotactic radiotherapy (92.24.4)^Citation35
Radiological examination	0.25 per month	100	125.28	CT of the most frequent metastatic sites:^Citation7 chest (87.41.1),^Citation35 upper abdomen (88.01.2),^Citation35 head (87.03.1),^Citation35 and upper-limbs (88.38.4)^Citation35
Post-progression
Palliative surgery, following cemiplimab	One time	8	1,895	DRG 272–273^Citation35
Palliative surgery, following chemotherapy	One time	3	1,895	DRG 272–273^Citation35
Oncologist visit	2 per month	100	20.66	General visit (89.7)^Citation35
GP visit	1 per month	100	20.66	General visit (89.7)^Citation35
Blood test	2 per month	100	5.75	Venous blood sampling (91.49.2)^Citation35 + blood count (90.62.2)^Citation35
Palliative RT	0.33 per month	45	987.75	Stereotactic radiotherapy (92.24.4)^Citation35
Complex palliative RT	0.33 per month	30	987.75	Stereotactic radiotherapy (92.24.4)^Citation35
Terminal care
At home	One time	39	3,798	Regione Veneto^Citation38
In hospital	One time	8	1,583	Zucco et al^Citation39
In hospice	One time	53	6,439	Ministero della Salute^Citation40

Table 4 AEs Rates and Costs for Cemiplimab and Chemotherapy

	Grade 3 and 4 AEs Rates (%)		Cost per Event (€)	Source
	Cemiplimab^Citation1	Chemotherapy^Citation26
Asthenia	2.60	0.00	1,787	DRG 463–464^Citation35
Hypokalemia	1.04	7.10	2,053	DRG 296–297^Citation35
Stomatitis or oral mucositis	0.00	8.60	585	Lazzaro et al^Citation42
Neutropenia	0.00	32.60	511	Mickisch et al^Citation43
Anemia	4.17	14.50	1,323	Mickisch et al^Citation43
Thrombocytopenia	0.00	7.70	1,323	Mickisch et al^Citation43
Febrile neutropenia	0.00	5.20	5,983	Brown et al^Citation44

Figure 2 Hazard of progression: comparison between base case and pessimistic scenario.

Table 5 Base-Case Results

	Cemiplimab	Chemotherapy	Cemiplimab vs Chemotherapy
Pre-progression costs (€)
1. Drugs	120,560	1,892	118,668
2. Monitoring	7,902	5,200	2,701
3. AEs	123	966	−843
4. Total	128,585	8,059	120,526
Post-progression costs (€)
5. Monitoring and terminal care	27,015	11,494	15,521
Lys
6. Pre-progression	1.82	1.18	0.65
7. Post-progression	6.05	1.80	4.24
8. Total	7.87	2.98	4.89
ICER (€/LY gained)	27,821
QALY
9. Pre-progression	1.58	1.02	0.56
10. Post-progression	4.88	1.46	3.43
11. Lost due to AEs	0.00	−0.006	0.006
12. Total	6.46	2.47	3.99
ICUR (€/QALY gained)	34,110

Figure 3 Cost-effectiveness acceptability curve.

Figure 4 Cost-effectiveness plane.

Table 6 Scenario Analysis Results

	Parameter	Base-Case	Scenario Analysis	ICER €/LY Gained	ICUR €/QALY Gained
	Base-case			27,821	34,110
1	Time horizon (years)	30	10	38,379	46,516
2	Time horizon (years)	30	20	28,697	35,150
3	Annual discount rate (%)	3	0	23,155	28,510
4	Annual discount rate (%)	3	5	31,056	37,972
5	Maximum duration of therapy (months)^a	22	Until progression	61,384	75,270
	And
	Extrapolation of PFS and OS hazard trend for cemiplimab	After 24 months, hazard trends increase linearly for 24 months to become equal to those of chemotherapy	Hazard trend is extrapolated based on the observed effects in the trial for the full-time horizon of the model
6	Age-related decrease in utility values	Estimated with a multiplier	Estimated with a difference	27,821	34,246
Pessimistic scenario analysis
7	Extrapolation of PFS and OS hazard trend for cemiplimab	After 24 months, hazard trends increase linearly for 24 months to become equal to those of chemotherapy	Equal to those of chemotherapy after 22 months	41,580	50,699
Naïve unanchored comparison
8	Method of modelling PFS and OS for cemiplimab	Simulated treatment comparison	Parametric models fitted to each intervention on observed data	38,139	46,630

Note: ^aThis assumption does not affect treatment efficacy but only treatment costs.

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