Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada

Figures & data

Figure 1 Partitioned model structure.

Table 1. Source of efficacy inputs.

Interventions	Details	n	Prior therapy	Outcomes (months)	Parameter functions	Reference
Ceritinib
SD	Pooled analysis from ASCEND-1 and ASCEND-2	303	1 or 2 lines prior chemotherapy, crizotinib	Median PFS = 6.7	Weibull	Novartis pooled analysis
Death				Median OS = 15.6
Comparators: Best supportive care
SD	Study comparing erlotinib vs BSC in patients who have had 2 prior lines of treatment	243	2 prior lines of chemotherapy	Median PFS = 1.8	Weibull	Shepherd et al.^36
Death				Median OS = 4.7
Comparators: Pemetrexed monotherapy
SD	Study comparing crizotinib vs pemetrexed/docetaxel in ALK + NSCLC in PROFILE 1007 study	99	1 prior line of chemotherapy	Median PFS = 4.3	Weibull	PROFILE1007, Shaw et al.^37
Death	Phase 3 study comparing pemetrexed and docetaxel in patients with NSCLC previously treated with chemotherapy	283	1 or 2 prior lines of chemotherapy	Median OS = 9.7		Hanna et al.^25
Comparators: Canadian historical controls (“historical controls, HC”)
SD	The PFS estimation was based on “physician defined PFS”, rather than PFS reported in clinical trials	25	Prior chemotherapy and ALK inhibitor	Median “physician defined” PFS = 1.3	Exponential	Canadian retrospective chart study^19
Death				Median OS = 1.7	Weibull
Comparators: Alternative scenario: Docetaxel
SD	Study comparing crizotinib vs pemetrexed/docetaxel in ALK + NSCLC in PROFILE 1007 study	72	1 prior line of chemotherapy	Median PFS = 2.5	Weibull	PROFILE1007, Shaw et al.^37
Death	Phase 3 study comparing best supportive care and docetaxel (75 mg/m^2) in patients with NSCLC previously treated with chemotherapy	55	1 or more lines of chemotherapy	Median OS = 7.6		Shepherd et al.^38 TAX317

HC, Historical controls; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; SD, stable disease.

Table 2. Summary of model inputs.

Parameters	Specification			Sensitivity analysis*	References
	Unit costs	Per cycle	Resource use
Unit costs of interventions
Ceritinib	$67.46	$8543	150 mg daily until progression, MDI of 83.2%	100% dose intensity	Dose intensity (relative mean dose) reported in ASCEND-1. Clinical study report^39
Pemetrexed	$2750	$7034	500 mg/m^2 over 10 min on the first day of each 21-day cycle, MDI of 98.6%	±10%	Regimens were retrieved from regimen monographs from Cancer Care Ontario, May 2014^40
Historical control	—	$2110	Weighted average of based on utilization reported in Canadian chart study	±10%	Unit costs of drugs were retrieved from DeltaPA^41
Docetaxel	$228	$2058	75 mg/m^2 in 1 h every 3 weeks, mean dose intensity of 92.6%	±10%
Administration costs				±25%
Pemetrexed	$139		Includes physician monitoring, length of patient visit, pharmacy workload, nursing workload
Docetaxel	$234
Physician visits
Medical oncologist	$157		44% of pts in SD, 75% in PD		Ontario Schedule of Benefits for Physician services, 2014^42
Radiation oncologist	$152		33% of pts in SD, 0% in PD
Pulmonologist	$157		22% of pts in SD, 25% in PD
Laboratory tests
Complete blood count	$10.59		75% of pts in SD, 100% in PD		Ontario schedule of laboratory services, 1999^43
Serum chemistry	$23.83		75% of pts in SD, 100% in PD
CT scan	$86.60		50% of pts in SD, 56% in PD		Ontario Schedule of Benefits for Physician services, 2014^42
X-Ray	$32.65		35% of pts in SD, 22% in PD
MRI	$73.35		15% of pts in SD, 22% in PD
Costs of active treatment in PD, ceritinib		$3394		±10%	Kayaniyil et al.^19
Costs of terminal care		$9001		±25%	Hollander^24
Costs of AEs					Derived from incidence of AE as reported in publications, For Docetaxel: Incidence reported for pemetrexed and pemetrexed + carboplatin
Ceritinib		$1285		Varied between 0 and 2× the base value
Pemetrexed		$1689			Unit costs were retrieved from Ontario Case Costing Initiative for inpatient and ambulatory care^44
HC		$2313
Docetaxel		$5212
Overall response adjusted utility-applied in stable disease	Utility estimate	Disutility estimate	Response rate applied		Utility estimate: obtained from Chouaid et al.^28
					Disutility estimate obtained from Nafees et al.^29
Ceritinib	0.629	−0.013	48.2%	Assume no response rate adjustment	Weighted average of ORR in ASCEND-1 and ASCEND-2
Pemetrexed	0.626	−0.015	29.3%		Shaw et al.^37
Docetaxel	0.621	−0.057	6.9%		Shaw et al.^37
Historical control arm	0.623	−0.015	15.1%		Weighted average of RR reported in retrospective study
Best supportive care	0.620	0.000	0.9%		Shepherd et al.^36

Sensitivity analysis*, Variations for one-way sensitivity analysis; MDI, Mean dose intensity; ORR, Overall Response Rate; RR, Response rate.

Table 3. Base case results.

	Ceritinib	Comparators
		BSC	Pemetrexed	HC
Total costs	$89,740	$10,686	$89,740	$17,658
Total QALYs	0.86	0.33	0.86	0.17
Total LYs	1.61	0.63	1.61	0.30
Incremental costs		$79,055	$34,906	$72,083
Incremental QALYs		0.53	0.44	0.69
Incremental LYs		0.98	0.86	1.31
ICER/QALY		$149,117	$80,100	$104,436
ICER/LY		$80,818	$40,748	$55,202

ICER, incremental cost effectiveness ratio; LY, life-years; QALY, qality-adjusted life years.

Table 4. Alternative scenarios.

	Scenario 1: Docetaxel	Scenario 2: Observed KM curves			Scenario 3: Utilities from PROFILE 1007
		BSC	Pemetrexed	HC	BSC	Pemetrexed	HC
Incremental costs	$67,541	$79,058	$34,904	$72,105	$79,055	$34,906	$72,083
Incremental QALYs	0.41	0.51	0.62	0.67	0.66	0.56	0.82
ICER/QALY	$149,780	$150,034	$79,278	$107,032	$119,926	$67,311	$87,695

Note: Utilities for HC is assumed to be similar to BSC.

ICER, incremental cost effectiveness ratio; QALY, quality-adjusted life years.

Figure 2 Results of one-way sensitivity analysis.

Figure 3 Incremental cost-effectiveness plane of ceritinib vs alternatives.

Figure 4 Visual fit of reconstructed and/or observed KM curves and parametric functions.

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