Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States

Figures & data

Figure 1.  Budget impact model structure. Model structure is based on current modeling standards for the budget impact of pharmaceutical products.

Table 1.  Target population inputs.

Target population input	Value	Source
Total plan population	1,000,000	Assumption
Proportion of female	50.8%	US Census 20109
Proportion of post-menopausal women (using the population 50 years and older as a proxy)	34.0%	US Census 20109; The proportion of women 50 years and older was used as a proxy for post-menopausal women10
Proportion of patients with breast cancer in the post-menopausal female population	3.5%	Proportion determined by combining the age-specific percentage of breast cancer patients obtained from SEER with US Census 2010 age-specific counts1,9
Proportion of patients with ABC	6.9%	Ho et al.11; The prevalence of ABC in post-menopausal women was assumed to be the same as that in women over the age of 20.
Proportion of HR+, HER2- ABC	58.3%	Carey et al.2; The proportion of HR+, HER2- among breast cancer patients was assumed to be the same as the proportion of HR+, HER2- among ABC patients
Proportion of HR+, HER2- ABC receiving letrozole or anastrozole	100%	Assumption
Proportion of patients with letrozole or anastrozole failure	70%	Johnston6
Patients on their first treatment option after   letrozole or anastrozole failure in a given year	42.3%	Baselga et al.7
Patients on their second treatment option after   letrozole or anastrozole failure in a given year	93.6%	Baselga et al.7; Assumption

Table 2.  Market share inputs.

Market share inputs	First treatment after letrozole or anastrozole failure	Second treatment after letrozole or anastrozole failure	Source
Rx market pre-everolimus entry
Exemestane	36.8%	28.5%	Data on file
Fulvestrant	44.7%	55.7%
Tamoxifen	18.6%	15.7%
Rx market post-everolimus entry
Exemestane	33.1%	25.7%	Data on file^a
Fulvestrant	40.2%	50.2%
Tamoxifen	16.7%	14.2%
Everolimus  + exemestane	10.0%	10.0%	Assumption

^aPost-entry market shares of treatments other than everolimus were estimated assuming that everolimus would replace each treatment proportional to their pre-entry market shares.

Table 3.  Pharmacy cost inputs.

Pharmacy inputs^a	Value	Source
Everolimus
WAC per dose (10 mg)	$267	ReadyPrice®12; Daily dose based on the everolimus product label8
Mean duration on medication (months)^b,c	7.8	Everolimus product label8
Average number of fills per year	8	Number of days on medication divided by 30, assuming each fill lasted for 30 days
Co-payment per fill	$40	Klepser et al.15
Dispensing fee per fill	$1.89	Mansley et al.16
Exemestane
WAC per dose (25 mg)	$6	ReadyPrice®12; Daily dose based on exemestane product label24
Mean duration on medication (months)^b,c	3.2	Everolimus product label8
Average number of fills per year	3	Number of days on medication divided by 30, assuming each fill lasted for 30 days
Co-payment per fill	$10	Klepser et al.15
Dispensing fee per fill	$1.89	Mansley et al.16
Fulvestrant (Intramuscular)
WAC per dose (500 ml)	$1704	ReadyPrice®12; Dose per injection based on fulvestrant product label, which specified injections of 500 ml three times in the first month and once monthly thereafter25
Mean duration on medication (months)^b,c	3.2	Assumed to be the same as exemestane based on the study by Chia et al.13
Average number of fills per year	5	Number of doses that a patient should take during the progression-free period
Co-payment per fill	$40	Klepser et al.15
Dispensing fee per fill	$1.89	Mansley et al.16
Tamoxifen
WAC per dose (20 mg)	$1	ReadyPrice®12; Daily dose based on tamoxifen product label26
Mean duration on medication (months)^b,c	6.7	Thurlimann et al.14
Average number of fills per year	7	Number of days on medication divided by 30, assuming each fill lasted for 30 days
Copayment per fill	$10	Klepser et al.15
Dispensing fee per fill	$1.89	Mansley et al.16

^aCompliance rates for all therapies were assumed to be 100% in the base case. ^bMedian PFS is used as a proxy for the mean duration on medication in a year. ^cMean time on treatment was assumed to be the same for first and second treatment options after failure with letrozole or anastrozole.

Table 4.  Medical cost inputs.

Medical cost inputs^a	Value	Source
Monthly charges associated with progression (2003 USD)	$9607	Lamerato et al.18
Monthly charges associated with non-progression (2003 USD)	$2356	Lamerato et al.18
Cost-to-charge ratio	0.454	Centers for Medicare & Medicaid Services19
Consumer price index from 2003 to 2011	1.34	Bureau of Labor Statistics data series. Consumer Price Index – All Urban Consumers17
Mortality
Everolimus + exemestane	17%	Mortality at a median follow-up of 12.5 months. Hortobagyi et al.20
Exemestane	23%	Mortality at a median follow-up of 12.5 months. Hortobagyi et al.20
Fulvestrant	23%	Assumed to be the same as exemestane
Tamoxifen	23%	Assumed to be the same as exemestane

^aCharges were converted to cost using cost-to-charge ratio (CCR) and then converted to 2011 US dollars using the medical component of the consumer price index (CPI)17,19.

Figure 2.  Budget impact for the first year of everolimus entry, (a) plan total, and (b) PMPM.

Figure 3.  One-way sensitivity analyses. ^aEverolimus plus exemestane market share: 20% market share as the second treatment option after letrozole or anastrozole failure.

Figure 4.  Two-way sensitivity analyses. (a) Target population size and everolimus cost. (b) Target population size and medical cost.

US Census Bureau. Table 1: intercensal estimates of the resident population by sex and age for the United States: April 1, 2000 to July 1, 2010 (US-EST00INT-01). US Census Bureau, Washington, DC, 2010

 Google Scholar

Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997;350:1047–59

 PubMed Web of Science ®Google Scholar

National Cancer Institute. SEER Cancer Statistics Review 1975-2008. SEER, 2011. http://seer.cancer.gov/csr/1975_2008/. Accessed October 24, 2011

 Google Scholar

Ho J, Zhang L, Todorova L, et al. Budget impact analysis of ixabepilone used according to FDA labeling in treatment-resistant metastatic breast cancer. J Manag Care Pharm 2009;15:467–75

 PubMed Web of Science ®Google Scholar

Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006;295:2492–502

 PubMed Web of Science ®Google Scholar

Johnston S. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res 2010;16:1979–87

 PubMed Web of Science ®Google Scholar

Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520–9

 PubMed Web of Science ®Google Scholar

Drug Topics RedBook. ReadyPrice Software, 2011. Access through MICROMEDEX 2.0; Thomson Reuters (Healthcare) Inc. Montvale, NJ. http://thomsonreuters.com/products_services/healthcare/healthcare_products/clinical_deci_support/micromedex_clinical_evidence_sols/med_safety_solutions/red_book/. Accessed February 22, 2012

 Google Scholar

U.S. Food and Drug Administration. Approved label for everolimus. FDA, Silver Spring, MD, 2012.   http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed on September 13, 2012

 Google Scholar

Klepser DG, Huether JR, Handke LJ, et al. Effect on drug utilization and expenditures of a cost-share change from copayment to coinsurance. J Manag Care Pharm 2007;13:765–77

 PubMed Web of Science ®Google Scholar

Mansley EC, Carroll NV, Chen KS, et al. Good research practices for measuring drug costs in cost-effectiveness analyses: a managed care perspective: the ISPOR Drug Cost Task Force report--Part III. Value Health 2010;13:14–17

 PubMed Web of Science ®Google Scholar

U.S. Food and Drug Administration. Approved label for exemestane. FDA, Silver Spring, MD, 2011. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed October 26, 2011

 Google Scholar

U.S. Food and Drug Administration. Approved label for Faslodex (Fulvestrant). FDA, Silver Spring, MD, 2011. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed October 26, 2011

 Google Scholar

Chia S, Gradishar W, Mauriac L, et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol 2008;26:1664–70

 PubMed Web of Science ®Google Scholar

U.S. Food and Drug Administration. Approved label for tamoxifen. FDA, Silver Spring, MD, 2011. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed October 26, 2011

 Google Scholar

Thürlimann B, Hess D, Köberle D, et al. Anastrozole ('Arimidex') versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind cross-over SAKK trial 21/95--a sub-study of the TARGET (Tamoxifen or 'Arimidex' Randomized Group Efficacy and Tolerability) trial. Breast Cancer Res Treat 2004;85:247–54

 PubMed Web of Science ®Google Scholar

Lamerato L, Havstad S, Gandhi S, et al. Economic burden associated with breast cancer recurrence: findings from a retrospective analysis of health system data. Cancer 2006;106:1875–82

 PubMed Web of Science ®Google Scholar

Centers for Medicare & Medicaid Services. Baltimore, MD. Statewide average operating cost-to-charge ratios for urban and rural hospitals (case weighted) March 2000. Medicare program: changes to the hospital inpatient prospective payment systems and fiscal year 2001 rates. http://www.federalregister.gov/articles/2000/08/01/00-19108/medicare-program-changes-to-the-hospitalinpatient-prospective-payment-systems-and-fiscal-year-2001#t-37. Accessed November 21, 2012

 Google Scholar

BLS data series. Consumer Price Index - All Urban Consumers. Washington, DC, 2012

 Google Scholar

Hortobagyi GN, Piccart M, Burris H, et al. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO-2 Phase III Trial. Thirty-Fourth Annual CTRC-AACR San Antonio Breast Cancer Symposium -- Dec 6--10, 2011; San Antonio, TX, SABCS abstracts 2011

 Google Scholar