Cost-effectiveness of lutetium (177Lu) oxodotreotide vs everolimus in gastroenteropancreatic neuroendocrine tumors in Norway and Sweden

Table 1 Drug acquisition costs for gastrointestinal-neuroendocrine tumors and pancreatic-neuroendocrine tumor

Treatment	Dose and frequency	Cost Sweden, SEK	Cost Norway, NOK
177Lu-Dotatate 7.4 GBq (Lutathera®)	4 administrations of 7.4 GBq, administered once every 8 wk	200000 per dose	228508 per dose
Octreotide LAR (Sandostatin®)	60 mg or 30 mg administered once every 28 d	11957.94 (30 mg) 23915.88 (60 mg)	13673 (30 mg) 27346 (60 mg)
Everolimus (Afinitor®)	10 mg once daily	38089.19 (1 × 30 tablet pack, 10 mg)	36525 (1 × 30 tablet pack, 10 mg)
Octreotide SC 50 μg/mL	If required	283.41 per dose	227.40 per dose
Granisetron1	3.1 mg/24 h depot patch administered prior to 177Lu-Dotatate	913.25 (1 × patch)	875.30
Ondansetron1	8 mg administered prior to 177Lu-Dotatate	1474.02 (1 × 30 tablet pack, 4 mg)	985.70 (1 × 30 tablet pack, 8 mg)
Tropisetron1	5 mg administered prior to 177Lu-Dotatate	1474.022	749.70 (1 × 5 tablet pack, 5 mg)
Vamin3	18%–18% infusion administered prior to/during 177Lu-Dotatate	458.08 (2 × 500 mL infusions)	202.8 (1 × 500 mL infusion)
Clinisol3	15% infusion administered prior to/during 177Lu-Dotatate	458.084	Not available in Norway

¹Anti-emetic required to be administered prior to administration with Lutathera.

²Cost assumed equal to ondansetron.

³Amino acid infusion required to be administered prior to and during administration of Lutathera.

⁴Cost assumed equal to Vamin. All Swedish costs are sourced from FASS (Pharmaceutical specialties in Sweden)[20]. All Norwegian costs are sourced from the Norwegian Medicines Agency[21]. PPP: Purchasing power parity; SC: Subcutaneous.

Table 2 Utilities used in the base case analysis

Health state	Utility (SE)	Source
Sweden
Midgut-NET progression-free survival	0.79 (0.01)	Real world evidence1
Midgut-NET post-progression survival	0.74 (0.01)	ERASMUS study2
P-NET progression-free survival	0.80 (0.01)	ERASMUS study2
P-NET post-progression survival	0.79 (0.02)	ERASMUS study2
Norway
Midgut-NET progression-free survival (Lutathera)	0.75 (0.01)	NETTER-1[13]
Midgut-NET post-progression survival	0.74 (0.01)	ERASMUS study2
P-NET progression-free survival	0.80 (0.01)	ERASMUS study2
P-NET post-progression survival	0.79 (0.02)	ERASMUS study2

¹Real world study conducted at Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom (AAA, data on file).

²AAA data on file. Midgut-NET: Midgut neuroendocrine tumor; P-NET: Pancreatic neuroendocrine tumor; SE: Standard error.

Table 3 Disutilities for grade 3 and 4 adverse events

Event	Disutility	Ref.
Nausea	0.05	Nafees et al[24]
Vomiting	0.05	Nafees et al[24]
Diarrhea	0.05	Nafees et al[24]
Abdominal pain	0.071	Doyle et al[25]
Thrombocytopenia	0.111	Tolley et al[26]
Lymphopenia	0.111	Assumed2
Leukopenia	0.111	Assumed2
Stomatitis	0.111	Assumed2
Fatigue	0.201	Swinburn et al[27]
Infections	0.111	Assumed2
Asthenia	0.201	Assumed3
Anemia	0.121	Swinburn et al[27]
Pyrexia	0.111	Assumed2
Hyperglycemia	0.111	Assumed2
Neutropenia	0.091	Nafees et al[24]
Hypertension	0.111	Assumed2
Musculoskeletal pain	0.111	Assumed2
Flushing	0.111	Assumed2
Decreased appetite	0.201	Assumed3

¹Standard error assumed to be equal to mean.

²Assumed.

³Assumed to be equal to fatigue.

Table 4 Summary of base case results

	177Lu-Dotatate	Everolimus	Delta
Sweden
Midgut-NETs
Total costs, SEK	1170 731	980913	189818
Quality-adjusted life expectancy, QALYs	3.45	2.97	0.48
ICER, SEK per QALY gained	391194
P-NETs
Total costs, SEK	1398533	1376035	22498
Quality-adjusted life expectancy, QALYs	4.90	3.55	1.35
ICER, SEK per QALY gained	16764
Norway
Midgut-NETs
Total costs, NOK	985062	653066	331995
Quality-adjusted life expectancy, QALYs	3.15	1.79	1.36
ICER, NOK per QALY gained	244444
P-NETs
Total costs, NOK	1280254	1056767	223487
Quality-adjusted life expectancy, QALYs	5.31	3.21	2.10
ICER, NOK per QALY gained	106451

NETs: Neuroendocrine tumors; QALY: Quality-adjusted life year; ICER: Incremental cost-effectiveness ratio; P-NET: Pancreatic-neuroendocrine tumor.

Table 5 Summary findings of budget impact analysis

	Year					Cumulative budget impact over 5 yr
	1	2	3	4	5
Sweden
Total treatment-eligible patients, n1	158	158	158	158	158	―
Projected market share for 177Lu-Dotatate, %2	30	60	80	90	90	―
Total cost if 177Lu-Dotatate adopted, SEK	85610153	102881530	114640765	120520382	120520382	544173212
Total cost if 177Lu-Dotatate not adopted, SEK	68338777	68338777	68338777	68338777	68338777	341693885
Budget impact, SEK	17271376	34542753	46301988	52181605	52181605	202479327
Norway
Total treatment-eligible patients, n1	100	100	100	100	100	―
Projected market share for 177Lu-Dotatate, %2	50	50	50	50	50	―
Total cost if 177Lu-Dotatate adopted, NOK	67920975	67920975	67920975	67920975	67920975	339604875
Total cost if 177Lu-Dotatate not adopted, NOK	44438750	44438750	44438750	44438750	44438750	222193750
Budget impact, NOK	23482225	23482225	23482225	23482225	23482225	117411125

¹Number of patients annually with metastatic GEP-NEPs based on an estimated incidence of 5.25 per 100000 population (Oberg et al[4], 2012) (40% of patients with GEP-NETs assumed to have metastases) and population estimates from national statistics agencies.

²Assumes that all other eligible patients are treated with everolimus.