Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States

Figures & data

Figure 1. Kaplan–Meier plots and long-term extrapolations of survival outcomes from KEYNOTE-177. Abbreviations. FA, final analysis; IA2, second interim analysis; KM, Kaplan–Meier; pembro, pembrolizumab; SoC, standard of care.

Table 1. Adverse event rates and durations from KEYNOTE-177.

Adverse event	Adverse event rates, %/week		Adverse event durations, days (SD)
	Pembrolizumab (%)	SoC (%)	Pembrolizumab	SoC
Abdominal pain	0.11	0.18	106.8 (135.81)	55.56 (67.67)
Anemia	0.09	0.32	64.13 (85.64)	126.5 (123.67)
Diarrhea	0.1	0.38	37.44 (54.06)	106.16 (231.72)
Fatigue	0.07	0.28	211.83 (250.13)	273.57 (325.92)
Hypertension	0.14	0.26	227.35 (328.05)	137.72 (210.47)
Hypokalemia	0.02	0.24	13 (12.73)	28.37 (42.2)
Hyponatremia	0.09	0.1	16.87 (9.87)	46.2 (42.89)
Neutropenia	0	0.56	NA	10.57 (6.74)
Neutrophil count decreased	0	0.69	NA	19.56 (15.99)

Abbreviations. n, number; NA, not applicable; SD, standard deviation; SoC, standard of care.

Table 2. Model inputs.

Parameter	Pembrolizumab	Standard of care	Uncertainty distribution	Source
Parametric survival model parameters	PFS (two-piece, 20 weeks, exponential) rate: ‒5.913	PFS (two-piece, 20 weeks, exponential) rate: ‒4.131	Varied with variance–covariance matrices	KEYNOTE-177
	OS (two-piece, 52 weeks, exponential) rate: ‒6.09	OS (two-piece, 52 weeks, exponential) rate: ‒5.606
		ToT (one-piece, exponential) rate: ‒3.626
Health state utility values by health state, mean (SE)	PF without Grade 3+ AEs: 0.881 (0.005)	PF without AEs: 0.845 (0.008)	Beta	KEYNOTE-177
	PF with Grade 3+ AEs: 0.843 (0.018)	PF with AEs: 0.812 (0.012)
	PD: 0.796 (0.011)
One-off QALY loss due to adverse events	0.00613	0.01966	Varies with health state utility values	Utility decrement was calculated from health state utility values from KEYNOTE-177. QALY loss calculated by multiplying utility decrement by duration of AEs from KEYNOTE-177.
Drug acquisition unit cost, USD	100 mg/vial: 4,862.04	5-fluorouracil 2,500 mg/ml: 11.9	Not varied	REDBOOK 2020^28
		Leucovorin 200 mg/ml: 10
		Oxaliplatin 50 mg/ml: 25
		Irinotecan 100 mg/ml: 18
		Cetuximab 100 mg/ml: 666.48
		Bevacizumab 100 mg/ml: 796.94
Drug administration costs, USD	IV push; single drug: 110.07		Normal*	CMS 2020^29
	IV infusion; up to 1 h: 142.55
	IV infusion; each additional hour (1–8 h): 30.68
	IV infusion; initiation of prolonged chemotherapy infusion (>8 h): 142.55
	IV infusion; each additional sequential infusion, up to 1 h: 69.29
Adverse event costs, USD (ICD-10 codes)	Abdominal pain: 6,961 (R10.9)		Normal*	HCUP 2017^6
	Anemia: 7,820 (D64.9)
	Diarrhea: 7,775 (R19.7)
	Fatigue: 8,020 (R53.83)
	Hypertension: 6,970 (I10)
	Hypokalemia: 7,508 (E87.6)
	Hyponatremia: 8,016 (E87.1)
	Neutropenia: 14,447 (D70.9)
	Neutrophil count decreased: 14,447 (D70.9)
Market shares of subsequent treatments, % of patients who received 2 L treatment	Pembrolizumab: 0%	Pembrolizumab: 68%	Varied in scenario analyses only	Market share data^30
	FOLFIRI: 100%	FOLFIRI: 22%
	Nivolumab: 0%	Nivolumab: 10%
Subsequent treatment durations, mean weeks	Pembrolizumab: 44.5		Not varied	Pembrolizumab and nivolumab assumed same as pembrolizumab in KEYNOTE-177; FOLFIRI assumed same as chemotherapies in KEYNOTE-177.
	FOLFIRI: 20.2
	Nivolumab: 44.5
Monitoring unit costs, USD	Consultant outpatient appointment: 80.91		Normal*	CMS 2020, 99211–99215: Average non-facility price for these codes^29
	Tumor marker test: 16.77			CMS 2020, 82105: Alpha-fetoprotein serum^29
	Liver function test: 8.17			CMS 2020, 80076: Hepatic function panel^29
	CT scan: 564.07			CMS 2020, 71275 and 74174: Sum of the payment rate for these codes^29
	Colonoscopy: 1,329.30			CMS 2020, 45378–45398: Average payment rate for these codes
	Inpatient care: 5,831.69			CMS 2008, Inpatient care for a short period to provide respite for primary caregiver per day^29, inflated to 2020 cost
Monitoring resource use in PF			Normal*	CMS manual
Consultant outpatient appointment	As per administration	Two every month
Tumor marker test	One every 3 months
Liver function test	One every 6 weeks	Two every month
CT scan	One every 6 months
Colonoscopy	One per year
Monitoring resource use in PD			Normal	CMS manual
Inpatient care	One day per month
Curative surgical resection unit cost, USD	1,839.42		Normal*	CMS 2020, 44140–44160: Colectomy traditional open procedure; 45110–45123: Proctectomy traditional open procedure; and 44204–44213, 45395 and 45397: Laparoscopic procedure^29
End of life unit costs, USD inflated to 2020 cost year	Inpatient cost: 28,439.35		Normal*	Chastek et al. (2012)^31
	Hospice care cost: 3,408.46
Productivity losses
Days of work lost due to disease (days per week)	PF: 0.307 days per week (8 working days lost every 6 months)		Normal*	Färkkilä et al. (2015)^32
	PD: 5 days per week			Assumption
Proportion of patients who retire early due to disease, %	12.8			Färkkilä et al. (2015)^32
Average salary (USD/hour)	62.20			Bureau of Labor Statistics^33

Abbreviations. AE, adverse event; CMS, Centers for Medicare & Medicaid Services; CT, computerized tomography; HCU, healthcare cost and utilization project; OS, overall survival; PD, progressed disease; PF, progression free; PFS, progression-free survival; QALY, quality-adjusted life year; SD, standard deviation; SE, standard error; ToT, time on treatment.

*Uncertainty data were not available and a standard error of 10% of the mean was assumed.

Table 3. Base case cost-effectiveness results.

Outcomes*	Pembrolizumab	Standard of care	Incremental
Total QALYs	4.845	3.232	1.614
Pre-progression	3.178	0.929	2.249
Post-progression	1.674	2.323	−0.649
AE decrement	−0.006	−0.020	0.014
Total LYs	5.939	4.124	1.815
Pre-progression	3.732	1.106	2.626
Post-progression	2.207	3.018	−0.811
Total costs (USD)	381,952	370,465	11,486
Drug acquisition	181,441	46,030	135,412
Administration	2,086	8,372	−6,286
Adverse events	2,699	10,950	−8,250
Surgery	172	171	1
Monitoring: progression-free	13,189	5,159	−149,275
Monitoring: progressed disease	154,434	211,192	56,758
Subsequent treatments	1,181	60,495	−59,314
End of life	26,344	28,098	−1,753
ICER (USD/QALY gained)	6,984
ICER (USD/LY gained)	6,211

Abbreviations. AE, adverse event; ICER, incremental cost-effectiveness ratio; LY, life year; QALY, quality-adjusted life year.

*Base case results are reported with 3.0% annual discounting of costs and health benefits.

Figure 2. Probabilistic sensitivity analysis. Abbreviations. QALY, quality-adjusted life year; WTP, willingness to pay.

Figure 3. Sensitivity and scenario analysis results. Abbreviations. AE, adverse event; BSC, best supportive care; LB, lower bound; NMB, net monetary benefit; PD, progressed disease; PF, progression free; SoC, standard of care; UB, upper bound; WTP, willingness-to-pay. Note: Base case NMB = $150,095.

IBM Corp. IBM Micromedex REDBOOK; 2020 [accessed May 2021]. Available from: https://www.micromedexsolutions.com/micromedex2/librarian/ssl/true.

 Google Scholar

Centers for Medicare & Medicaid Services. Physician fee schedule search; 2020 [updated 2021 Jan 20; accessed May 2021]. Available from: https://www.cms.gov/apps/physician-fee-schedule/search/search-criteria.aspx.

 Google Scholar

Agency for Healthcare Research and Quality. Healthcare cost and utilization project; 2017 [accessed May 2021]. Available from: https://hcupnet.ahrq.gov/#setup.

 Google Scholar

IQVIA. MSI/MMR Treatment. 2020. Data on file.

 Google Scholar

Chastek B, Harley C, Kallich J, et al. Health care costs for patients with cancer at the end of life. J Oncol Pract. 2012;8(6):75s–80s.

 PubMedGoogle Scholar

Färkkilä N, Torvinen S, Sintonen H, et al. Costs of colorectal cancer in different states of the disease. Acta Oncol. 2015;54(4):454–462.

 PubMed Web of Science ®Google Scholar

U.S. Bureau of Labor Statistics. Employer costs for employee compensation – March 2021; 2021 [accessed 2021 Aug 13]. Available from: https://www.bls.gov/news.release/pdf/ecec.pdf.

 Google Scholar