The cost-effectiveness of alectinib in anaplastic lymphoma kinase-positive (ALK+) advanced NSCLC previously treated with crizotinib

Figures & data

Table 1. Comparison of alectinib and ceritinib trial data.

	ASCEND I^a^,^16	ASCEND II^c^,^14	NP28673^d^,^17^,^18	NP28761^e^,^13^,^21
	n (%; 95% CI)	n (%; 95% CI)	n (%; 95% CI)	n (%; 95% CI)
Study population characteristics
Study population size	163	140	138	87
Age (median, years)	52	51	52	54
Sex (% female)	88 (54%)	70 (50%)	77 (56%)	48 (55%)
ECOG or WHO performance status (≤1)	142 (87%)	120 (86%)	125 (91%)	78 (90%)
Prior chemotherapy	116 (71%)	140 (100%)	110 (80%)	64 (74%)
Baseline CNS metastases	98 (60%)	100 (71%)	84 (61%)	52 (60%)
Clinical outcomes
Objective response rate	75 (46%; 38–54)^b	50 (49%; 39–59)	62 (51%; 42–60)	35 (52%; 40-65)
Disease control rate	121 (74%; NA)^b	87 (85%; 77–92)	96 (79%; 70–86)	53 (79%; NA)
Median PFS (months)	7.0 (5.7–8.7)^b	7.2 (5.4–9.0)	8.9 (5.6–12.8)	8.1 (6.2–12.6)
Median duration of response (months)	8.8 (6.0–13.1)^b	9.7 (5.6–12.9)	14.1 (10.9–NR)	13.5 (6.7–NR)
Median OS (months)	16.7 (14.8–NR)	14.9 (13.5–NR)	NR	NR
OS at 12 months (%)	67 (59–74)	NA	NA	71 (61–81)
Median follow-up time, months (range)	11.1 (6.7–15.2)	11.3 (0.1–18.9)	14.5 (0.6–20.5)	9.9 (6.2–12.9)

ECOG, Eastern Cooperative Oncology Group; CNS, central nervous system; PFS, progression free survival; OS, overall survival; NA, not available.

^a Based on data from crizotinib pre-treated patients (data cut: April 14, 2014)¹⁶.

^b Blinded independent review committee assessed.

^c Based on blinded independent review committee assessed data, response outcomes limited to per protocol population (n = 102) (data cut: August 13, 2014)¹⁴.

^d Based on independent review committee assessed data from updated data set (data cut: April 27, 2015), response data limited to response evaluable population (n = 122)¹⁷.

^e Based on independent review committee assessed data from latest data cut (date: April 27, 2015), response data limited to response evaluable population (n = 69)^13,21.

Figure 1. Model structure.

Table 2. Grade 3/4 adverse event rates^a and costs^20,26–29.

Adverse event	Cost per event	Alectinib		Ceritinib
Anemia	$2,762	2%	$55.24	5%	$140.86
Fatigue	$208	1%	$2.50	5%	$10.63
Infection (including pneumonia)	$9,575	0%	$0.00	5%	$450.01
Nausea	$208	0%	$0.00	6%	$12.29
Diarrhea	$208	1%	$2.50	6%	$12.29
Vomiting	$4,339	0%	$17.36	5%	$203.93
Hyperglycemia	$208	2%	$4.17	6%	$12.29
Lipase increase	$208	0%	$0.00	6%	$13.13
Blood alkaline increase	$208	1%	$2.50	5%	$10.63
Total			$84.26		$866.07

^a Adverse events were assumed to occur during the first month of treatment.

Table 3. Model inputs.

	Input	Low	High	Distribution	Source
Utilities
Utility: Alectinib PF	0.79	0.71	0.87	Beta	^23
Utility: Ceritinib PF	0.73	0.66	0.80	Beta	^30
Utility: Disease progression	0.46	0.41	0.51	Beta	^31^,^32
Cost inputs
Alectinib drug cost	$51	$46	$56	Normal^a	^26
Ceritinib drug cost	$96	$86	$105	Normal	^26
Valsartan	$44	$39	$48	Normal	^26
Pegfilgrastim, 0.6 mL syringe	$5156	$4640	$5671	Normal	^26
Epoetin alfa, vial	$32	$29	$35	Normal	^26
Prednisone	$21	$19	$23	Normal	^26
Cost continuing care (per month)	$750	$675	$825	Normal	^34
Cost terminal care (per month)	$8956	$8060	$9851	Normal	^34
Cost of Chest CT (CPT: 71260)	$231	$208	$254	Normal	^28
Cost of Brain CT (CPT: 70460)	$105	$95	$116	Normal	^28
Follow-up Consultation (CPT code 99215)	$208	$131	$160	Normal	^28
Outpatient Consultation (CPT code 99205)	$208	$188	$229	Normal	^28
Platelet Transfusion (CPT code 36430)	$6427	$5784	$7070	Normal	^36
ER Visit (CPT code 99285)	$175	$158	$193	Normal	^28
IV infusion per hour (CPT code 96413)	$136	$123	$150	Normal	^28
Subcutaneous or intramuscular injection (CPT code 96372)	$25	$23	$28	Normal	^28
Inpatient Stay: Complications from treatment	$8261	$7435	$9087	Normal	^28^,^37
Inpatient Consultation on Admission Day (CPT code 99254)	$169	$152	$186	Normal	^28
Inpatient Physician Fee (CPT code 99252)	$76	$68	$83	Normal	^28
Inpatient Consultation on Discharge Day (CPT code 99217)	$73	$66	$81	Normal	^28
Inpatient Stay: Respiratory Illness with Complications	$11,177	$10,059	$12,294	Normal	^28^,^37
Inpatient Stay: Respiratory Illness with Major Complications	$7973	$7176	$8770	Normal	^28^,^37
Treatment for vomiting	$4339	$3905	$4773	Normal	^28^,^37

^a Values limited to positive values.

PF: progression-free; CT: computerized tomography; CPT: current procedural terminology; ER: emergency room; IV: intravenous.

Table 4. Results for cost utility analysis.

	Pre-progression cost	Post-progression cost	Total cost	LYs	QALYs
Alectinib	$153,189	$102,224	$255,413	2.39	1.42
Ceritinib	$143,662	$97,883	$241,545	1.67	0.98
Difference	$9527	$4341	$13,868	0.72	0.44
ICER				$19,313	$31,180

Figure 2. Cost-effectiveness acceptability curve.

Figure 3. Tornado diagram of one-way sensitivity analysis.

Table A1. Healthcare resources and costs to treat adverse events^20,26–29.

Side effect	Treatment assumptions and cost of treatment	Total event cost
Anemia	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208 50% of patients treated with 40K units of epoetin weekly for 8 weeks Cost of epoetin alfa 2K units = $32	$2762
Fatigue	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208
Infection (including pneumonia)	50% of patients have major complications DRG 178: Treatment of respiratory infection with complications = $7973 DRG 177: Cost of inpatient stay for respiratory stay with major complications = $$11,177	$9575
Nausea	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208
Diarrhea	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208
Vomiting	DRG 392: Esophagitis, gastroenteritis and miscellaneous digestive disorders without major complications or comorbidities	$4339
Hyperglycemia	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208
Lipase increase	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208
Blood alkaline increase	1 outpatient physician office visit Cost of 1 outpatient physician visit = $208	$208

Table A2. Parameter inputs.

Efficacy endpoint	Alectinib treatment arm	Ceritinib treatment arm
Progression free survival (Weibull)
Lambda	0.0673	0.0575
Gamma	1.0601	1.3087
Overall survival (Weibull)
Lambda	0.0192	0.0184
Gamma	1.1261	1.2804

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