Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data

Figures & data

Figure 1. Partitioned survival model structure. CP: chronic phase; AP: accelerated phase; BC: blast crisis.

Figure 2. Projected time on treatment, progression-free survival, and overall survival (including natural mortality). (A) Nilotinib (exponential parametric function). (B) Dasatinib (exponential parametric function). OS: overall survival; PFS: progression-free survival; TOT: time on treatment.

Table 1. Base-case model inputs.

Input	Value	Notes/References
CML-related drug costs
CP on treatment (per month)	Nilotinib: $8,818.19	Unit costs based on the 2015 Red Book^30, with an average starting dose from Griffin et al.^16, assuming 100% adherence rate^10^,^11.
	Dasatinib: $12,041.58
CP post-discontinuation (per month)	For nilotinib-treated patients: $10,195.69	Treatments included: dasatinib, bosutinib, ponatinib, interferon alpha, and omacetaxine^8; unit costs based on the 2015 Red Book^30; proportions were estimated based on a physician survey^31.
	For dasatinib-treated patients: $10,196.87	Treatments included: nilotinib, bosutinib, ponatinib, interferon alpha, and omacetaxine^8; unit costs based on the 2015 Red Book^30; proportions were estimated based on a physician survey^31.
Progressive disease	Monthly cost: $7,233.73	Treatments included: bosutinib, ponatinib, interferon alpha, and omacetaxine^8; unit costs based on the 2015 Red Book^30; proportions were estimated based on a physician survey^31.
	One-time cost: $47,254.41	Treatments included chemotherapy and bone marrow transplant^8; unit cost of chemotherapy was based on a claims database analysis^31, while unit cost of bone marrow transplant was based on Maziarz et al.^35; proportions were estimated based on a physician survey^31.
Medical costs
Monitoring and resource utilization costs (per month)	CP on treatment: $552.72 CP post-discontinuation: $552.72Progressive disease: $2,230.73	Monitoring costs The types of monitoring tests were based on NCCN guidelines^8; the unit costs of monitoring tests were obtained from the CMS Physician Fee Schedule^36; the frequencies of monitoring tests for CP on treatment were obtained from Goldberg et al.^37, and frequencies of monitoring tests specific to CP post-discontinuation or progressive disease were assumed to be the same as those for CP on treatment.
		Resource utilization costs The types of resources used were based on Reed et al.^38; the unit costs of resources used were based on the CMS Physician Fee Schedule^36 and Reed et al.^38; the frequencies of resources used for CP on treatment and progressive disease were based on Reed et al.^38, and frequencies of resources used specific to CP post-discontinuation was assumed to be the same as those for CP on treatment.
Terminal care costs for the last month before death	$82,014.77	Based on Yabroff et al.^39.
AE costs (per month up to 24 months in CP on treatment)	Nilotinib: $396.13Dasatinib: $305.13	Grade 3/4 AEs included those occurring in ≥5% patients treated with either second-line nilotinib or dasatinib over a 24-month timeframe; the proportion of patients experiencing AEs for nilotinib and dasatinib were obtained from Kantarjian et al.^40 and Shah et al.^15, respectively; AE unit costs were obtained from Liou et al.^41 or HCUPnet^42.
Utility	CP on treatment: 0.82CP post-discontinuation: 0.82Progressive disease: 0.53	Utility inputs for CP on treatment and progressive disease were obtained from Szabo et al.^28; utility for CP post-discontinuation was assumed to be the same as that for CP on treatment.

CML: chronic myeloid leukemia; CP: chronic phase; LY: life years; QALY: quality-adjusted life years; AE: adverse event; NCCN: National Comprehensive Care Network; CMS: Center for Medicare and Medicaid Services.

Table 2. Base-case results.

	Nilotinib	Dasatinib	Nilotinib vs Dasatinib
Costs (in 2015 USD)
Treatment costs	$1,238,256	$1,258,947	−$20,691
CP on treatment	$917,086	$999,406	−$82,320
CP post-discontinuation	$181,380	$104,278	$77,102
Progressive disease	$139,790	$155,264	−$15,474
Medical costs	$162,623	$156,762	$5,861
CP on treatment	$57,483	$45,948	$11,535
CP post-discontinuation	$9,833	$5,653	$4,180
Progressive disease	$41,746	$46,270	−$4,524
Death (terminal care cost)	$53,562	$58,891	−$5,329
AE costs	$8,587	$6,413	$2,174
Total costs	$1,409,466	$1,422,122	−$12,655
Effectiveness
Total LYs	11.7	9.5	2.2
CP on treatment	8.7	6.9	1.7
CP post-discontinuation	1.5	0.9	0.6
Progressive disease	1.6	1.7	−0.2
Total QALYs	9.1	7.3	1.9
CP on treatment	7.1	5.7	1.4
CP post-discontinuation	1.2	0.7	0.5
Progressive disease	0.8	0.9	−0.1
Incremental cost-effectiveness ratio (ICER)	Nilotinib was associated with a higher number of LY (difference: 2.2) and QALY (difference: 1.9), and lower costs (difference: $12,655) vs dasatinib

CP: chronic phase; LY: life years; QALY: quality-adjusted life years; USD: United States dollars.

Table 3. Deterministic sensitivity analysis results.

Model input	Variation	Parameter	Base-case input	DSA input	DSA ICER per QALY (Nilotinib vs Dasatinib)
Starting age	+5 years	Starting age	60	65	Dominant*
	−5 years	Starting age	60	55	$10,095
% female	+10% absolute points	% female	35%	45%	Dominant
	−10% absolute points	% female	35%	25%	Dominant
Adherence for both drugs	Assume 80% adherence for both drugs	Nilotinib adherence	100%	80%	$2,055
		Dasatinib adherence	100%	80%
CP post-discontinuationdrug treatment costs	20%	Nilotinib monthly costDasatinib monthly cost	$10,196$10,197	$12,235$12,236	$1,492
	−20%	Nilotinib monthly cost	$10,196	$8,157	Dominant
		Dasatinib monthly cost	$10,197	$8,157
Progressive disease drug treatment costs	20%	Recurrent monthly costOne-time cost	$7,234$47,254	$8,680$56,705	Dominant
	−20%	Recurrent monthly cost	$7,234	$5,787	Dominant
		One-time cost	$47,254	$37,804
Medical costs	20%	CP on treatment	$553	$663	Dominant
		CP post-discontinuation	$553	$663	Dominant
		Progressive disease	$2,231	$2,677	Dominant
	−20%	CP on treatment	$553	$442	Dominant
		CP post-discontinuation	$553	$442	Dominant
		Progressive disease	$2,231	$1,785	Dominant
AE costs	20%	Nilotinib AE cost	$396	$475	Dominant
		Dasatinib AE cost	$305	$366
	−20%	Nilotinib AE cost	$396	$317	Dominant
		Dasatinib AE cost	$305	$244
Utility for CP post-discontinuation	−0.1 absolute points	CP post-discontinuation utility	0.82	0.72	Dominant

DSA: deterministic sensitivity analysis; ICER: incremental cost-effectiveness ratios; QALY: quality-adjusted life years; AE: adverse events; CP: chronic phase.

* “Dominant” indicates nilotinib was associated with better QALY and lower costs vs dasatinib.

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