Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives

Figures & data

Figure 1 Model structure.

Abbreviations: w/o, without; w/, with; AE, adverse event; UC, urothelial cancer.

Table 1 Market Share With And Without Uptake Of Avelumab As 2L Therapy

Treatment	Market Shares In World Without Avelumab			Market Shares In World With Avelumab
	Year 1	Year 2	Year 3	Year 1	Year 2	Year 3
Avelumab	0.0%	0.0%	0.0%	1.7%	1.2%	1.0%
Atezolizumab	9.4%	7.0%	5.4%	9.1%	6.8%	5.3%
Durvalumab	1.1%	0.8%	0.6%	1.1%	0.8%	0.6%
Nivolumab	16.5%	12.3%	9.6%	16.0%	11.9%	9.3%
Pembrolizumab	28.1%	20.9%	16.3%	27.2%	20.3%	15.8%
CT	45.0%	59.0%	68.0%	45.0%	59.0%	68.0%
Total	100.0%	100.0%	100.0%	100.0%	100.0%	100.0%

Abbreviations: 2L, second-line; CT, chemotherapy.

Table 7 Results Of Sensitivity Analyses – Budget Impact Over 3-Year Time Horizon

Scenarios	Commercial Perspective			Medicare Perspective
	Incremental Budget Impact (2018 US$)	Change In Budget (%)	Incremental PMPM (2018 US$)	Incremental Budget Impact (2018 US$)	Change In Budget (%)	Incremental PMPM (2018 US$)
Base case	$73,438	<1%	$0.000	$719,324	<1%	$0.002
Treatment duration based on mean PFS	-$50,162	<1%	$0.000	$443,990	<1%	$0.001
Treatment duration based on median treatment duration observed in the clinical trials	-$16,722	<1%	$0.000	$306,590	<1%	$0.001
Number of patients eligible for 2L treatment increased by 20%	$88,126	<1%	$0.000	$863,189	<1%	$0.002
Number of patients eligible for 2L treatment decreased by 20%	$58,751	<1%	$0.000	$575,459	<1%	$0.002
AE management costs increased by 30%	$74,757	<1%	$0.000	$726,622	<1%	$0.002
AE management costs decreased by 30%	$72,120	<1%	$0.000	$712,026	<1%	$0.002
Disease management costs increased by 30%	$83,264	<1%	$0.000	$723,451	<1%	$0.002
Disease management costs decreased by 30%	$63,613	<1%	$0.000	$715,198	<1%	$0.002
Costs included in the analysis limited to 2L drug costs only	$1,969	<1%	$0.000	$436,357	<1%	$0.001
Avelumab market share remains consistent after year 1 (1.7%)	$94,667	<1%	$0.000	$927,254	<1%	$0.003

Abbreviations: PMPM, patient member per month; PFS, progression-free survival; 2L, second line; AE, adverse event; mUC, metastatic urothelial carcinoma; USD, United States Dollars.

Table 2 Dosing, Duration, Drug And Administration Costs

A. Dose, Cycle Length, Cost Per Cycle And Treatment Duration
Treatment	Dose		Cycle Length (Weeks)	Drug Cost Per Cycle (Commercial; US$)		Drug Cost Per Cycle (Medicare; US$)	Median Treatment Duration (Months)
Avelumab	800 mg		2	$7,437		$7,884	2.8
Atezolizumab	1200 mg		3	$10,657		$11,296	2.8
Nivolumab	240 mg		2	$7,552		$6,517	2.8
Pembrolizumab	200 mg		3	$11,159		$9,715	2.8
Durvalumab	10 mg/kg		2	$7,066		$7,425	2.8
Carboplatin	4.5 AUC		4	$100		$52	2.1
Gemcitabine	1000 mg/m^2		4	$452		$227	2.1
Docetaxel	100 mg/m^2		3	$1,080		$420	2.1
Paclitaxel	150 mg/m^2		2	$155		$52	2.1
Pemetrexed	500 mg/m^2		3	$12,177		$7,871	2.1
B. Monthly Drug & Administration Costs
Commercial Perspective
Treatment		Monthly Drug Costs, US$			Monthly Administration Costs, US$
Avelumab		$16,170			$1,161
Atezolizumab		$15,446			$774
Nivolumab		$16,418			$1,161
Pembrolizumab		$16,174			$774
Durvalumab		$15,362			$1,161
Carboplatin		$3,508			$1,462
Gemcitabine		$3,508			$1,462
Docetaxel		$3,508			$1,462
Paclitaxel		$3,508			$1,462
Pemetrexed		$3,508			$1,462
Medicare Perspective
Treatment		Monthly Drug Costs, US$			Monthly Administration Costs, US$
Avelumab		$17,140			$608
Atezolizumab		$16,373			$405
Nivolumab		$14,169			$608
Pembrolizumab		$14,081			$405
Durvalumab		$16,142			$608
Carboplatin		$2,143			$765
Gemcitabine		$2,143			$765
Docetaxel		$2,143			$765
Paclitaxel		$2,143			$765
Pemetrexed		$2,143			$765

Table 3 Percentage Of Patients Experiencing Grade ≥3 Adverse Events And Total Adverse Event Costs

Grade ≥3 Adverse Events	Avelumab^Citation25	Atezolizumab^Citation26	Nivolumab^Citation28	Pembrolizumab^Citation29	Durvalumab^Citation27	CT^Citation31
Fatigue	7.0%	6.0%	7.0%	4.5%	6.0%	4.3%
Constipation	1.0%	0.3%	0.4%	1.1%	1.0%	3.1%
Abdominal pain	2.0%	4.0%	1.5%	1.1%	3.0%	0.0%
Hypertension	5.0%	0.0%	0.0%	0.0%	0.0%	0.0%
Urinary tract infection	5.0%	9.0%	7.0%	4.9%	4.0%	0.0%
Increased lipase	6.0%	0.0%	7.0%	0.0%	0.0%	0.0%
Increased alkaline phosphatase	7.0%	4.0%	5.5%	7.0%	4.0%	0.0%
GGT increased	12.0%	0.0%	0.0%	0.0%	0.0%	0.0%
Hyperglycemia	9.0%	5.0%	2.4%	8.0%	3.0%	0.0%
Anemia	6.0%	8.0%	7.0%	13.0%	8.0%	7.8%
Lymphopenia	11.0%	10.0%	9.0%	15.0%	11.0%	0.0%
Thrombocytopenia	0.0%	0.0%	2.4%	0.0%	0.0%	0.0%
Neutropenia	0.0%	0.0%	0.0%	0.0%	1.0%	13.3%
Febrile neutropenia	<0.1%	<0.1%	<0.1%	<0.1%	<0.1%	<0.1%
Hyponatremia	16.0%	10.0%	11.0%	9.0%	12.0%	0.0%
Increased ALT/AST	3.9%	4.0%	4.7%	4.1%	2.6%	0.0%
Increased bilirubin	1.0%	0.0%	0.0%	0.0%	0.0%	0.0%
Hepatitis	0.8%	2.9%	0.7%	0.5%	0.5%	0.0%
Pneumonitis	0.4%	0.7%	1.1%	1.3%	0.0%	0.0%
Colitis	0.4%	1.4%	0.7%	1.2%	0.0%	0.0%
Thyroid disorders	0.2%	0.0%	0.0%	0.0%	0.0%	0.0%
Hypothyroidism	0.0%	0.0%	0.0%	0.1%	0.0%	0.0%
Hyperthyroidism	0.0%	0.0%	0.0%	0.1%	0.0%	0.0%
Diabetes mellitus	0.1%	0.0%	0.0%	0.0%	0.0%	0.0%
Rash	0.4%	0.3%	1.5%	0.4%	0.5%	1.2%
Total Cost for Adverse Event Management per Therapy (Commercial Perspective; US$)	$1,515	$1,634	$1,108	$971	$1,076	$49
Total Cost for Adverse Event Management per Therapy (Medicare Perspective; US$)	$1,438	$1,448	$1,017	$906	$1,017	$55

Abbreviations: CT, chemotherapy; GGT, gamma-glutamyl transferase; ALT, alanine aminotransferase; AST, aspartate transaminase.

Table 4 Healthcare Resource Costs Of Adverse Event Management

Type Of Resource Use	Unit Cost (Commercial Perspective; US$)	Unit Cost (Medicare Perspective; US$)	Source
Oncologist visit	$119	$109	35–37
Endocrinologist visit	$182	$167	35–37
Full blood count	$21	$8	35–37
Liver function test	$27	$10	35–37
Renal function test	$28	$11	35–37
Thyroid function test	$21	$21	35–37
LDH test	$20	$7	35–37
Transfusion administration	$390	$390	35–37
Blood unit for transfusion (outpatient)	$415	$415	39
Platelet unit for transfusion (outpatient)	$645	$645	39
IV fluid (500 mL; outpatient)	$2	$2	23
Hospitalization – Constipation	$5,937	$7,104	38
Hospitalization - Abdominal pain	$6,755	$7,068	38
Hospitalization – Hyperglycemia	$4,558	$6,510	38
Hospitalization - Febrile neutropenia	$12,544	$18,617	38
Hospitalization – Hyponatremia	$7,531	$7,150	38
Hospitalization – Hepatitis	$26,373	$21,690	38
Hospitalization – Pneumonitis	$23,213	$14,614	38
Hospitalization – Colitis	$23,213	$14,614	38
Hospitalization - Diabetes mellitus	$9,489	$11,834	38

Abbreviations: LDH, lactic acid dehydrogenase; IV, intravenous; mL, milliliter.

Table 5 Disease Management Costs

Monthly Cost Of Disease Management	Monthly Costs (Commercial Perspective; US$)	Monthly Costs (Medicare Perspective; US$)
Pre-progression/on-treatment	Avelumab: $2,130 Atezolizumab: $1,959 Nivolumab: $2,130 Pembrolizumab: $1,959 Durvalumab: $2,130 CT: $2,165	Avelumab: $1,307 Atezolizumab: $1,186 Nivolumab: $1,307 Pembrolizumab: $1,186 Durvalumab: $1,307 CT: $1,317
Post-progression/on subsequent active treatment (CT)	$2,093	$1,351
Post-progression/off-treatment (BSC)	$2,611	$2,414
Post-progression/off-treatment (BSC, one-time cost)	$121	$48

Abbreviations: BSC, best supportive care; CT, chemotherapy.

Figure 2 Budget impact of avelumab in the treatment of locally advanced or mUC (A) Commercial perspective and (B) Medicare perspective (US$).

Abbreviation: UC, urothelial carcinoma.

Table 6 Budget Impact Over 3-Year Time Horizon

Costs, US$	Current Market Mix	Revised Market Mix	Cumulative Budget Impact	Change In Budget (%)*
Commercial Perspective
Drug and Administration Costs	$39,778,374	$39,814,667	$36,293	0.09%
AE Management Costs	$449,928	$454,323	$4,395	0.98%
Disease Management Costs	$30,039,733	$30,072,483	$32,750	0.11%
Total	$70,268,035	$70,341,473	$73,438	0.10%
Cost PMPM	$0.20	$0.20	$0.00	0.10%
Medicare Perspective
Drug and Administration Costs	$155,409,042	$155,954,655	$545,613	0.35%
AE Management Costs	$2,222,797	$2,247,124	$24,327	1.09%
Disease Management Costs	$135,291,260	$135,440,644	$149,384	0.11%
Total	$292,923,098	$293,642,422	$719,324	0.25%
Cost PMPM	$0.81	$0.81	$0.00	0.25%

Note: *Due to rounding, these numbers cannot be replicated.

Abbreviations: AE, adverse event; PMPM, per member per month.

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