ISPOR poster

1. Budget Impact of Ribociclib Plus Letrozole for Treatment-Naive
Post-Menopausal Women With HR+/HER2- Advanced or
Metastatic Breast Cancer From a US Third-Party Payer Perspective
Mistry R,1
Suri G,1
Young KC,1
Hettle R,1
May JR,1
Brixner D,2
Oderda G,2
Biskupiak J,2
Tang D,3
Bhattacharyya D,4
Bhattacharyya S,4
Mishra D,4
Dalal A3
*
1
PAREXEL, London, UK; 2
University of Utah, Salt Lake City, UT, USA; 3
Novartis, East Hanover, NJ, USA; 4
Novartis, Hyderabad, Telangana, India
*Corresponding author (anand.dalal@novartis.com)
Background
• Treatmentoptionsforhormonereceptor-positive(HR+),humanepidermal
growthfactorreceptor2-negative(HER2-)advancedormetastaticbreast
cancerinpost-menopausalpatientsincludearomataseinhibitors(e.g.,
letrozole),selectiveestrogenreceptormodulators(e.g.,tamoxifen),estrogen
receptorantagonists(e.g.,fulvestrant)and,mostrecently,theoral,highly-
selective,cyclin-dependentkinase4and6(CDK4/6)inhibitorsribociclib
(KISQALI®
;Novartis)andpalbociclib(IBRANCE®
;PfizerInc.)1,2
• Clinical studies have shown that the combination of a CDK 4/6 inhibitor
with letrozole is a tolerable, safe and efficacious alternative to letrozole
monotherapy for first-line HR+/HER2- advanced breast cancer3-5
Objective
• To estimate the budget impact of introducing ribociclib + letrozole as a
first-line treatment option for post-menopausal patients with HR+/HER2-
advanced or metastatic breast cancer in the United States from a third-
party payer perspective
Methods
Model Structure
• A cohort-based budget impact model was developed using Microsoft
Excel®
2010 to calculate the incremental cost of introducing ribociclib
+ letrozole over 3 years for a target population of treatment-naïve post-
menopausal patients with HR+/HER2- advanced or metastatic breast
cancer (Table 1)
• Direct medical costs related to treatment acquisition, treatment
administration, treatment monitoring, adverse events, and subsequent
therapy were included
• The model compared two scenarios: treatment options for this patient
population excluding ribociclib + letrozole versus a scenario where
ribociclib + letrozole was included
• Three lines of therapy were included, as this was the expected average
number of lines of therapy this patient population would receive. In
alignment with the ASCO guideline on endocrine therapy6
, patients who
received CDK 4/6 inhibitor in the first-line setting were assumed not to
receive a subsequent CDK inhibitor
Table 1. Model Cohort Characteristics
Cohort
characteristics
A hypothetical cohort of 1,000,000 health plan members:
• Female: 50.8%7
• Post-menopausal (age ≥50 years): 33.9%7
• Post-menopausal with breast cancer: 3%8
• Proportion with advanced/metastatic breast cancer:
6.9%9
• HR+/HER2- subtype: 74%9
• HR+/HER2- patients eligible for CDK 4/6 inhibitor
treatment: 100%
Sources: See table content.
First-line Treatment
• Market shares for treatments in both scenarios were supported by market
research (user modifiable) (Figure 1)
• The launch of CDK 4/6 inhibitors is assumed to derive market share from
existing therapies, from 47.7% in Year 1 to 64.6% in Year 3
• Ribociclib was assumed to gain market share from palbociclib (Year 1
onwards); the market share of ribociclib + letrozole increased from 3.3% in
Year 1 to 19.3% in Year 3
• Treatment duration was based on the median time to treatment
discontinuation (TTD) or median PFS5,10-13
Figure 1. Treatment Market Shares in Year 1 for Scenario Including
Ribociclib + Letrozole
Ribociclib + Letrozole, 3%
Palbociclib + Letrozole,
36%
Letrozole, 7%
Fulvestrant, 6%
Exemestane, 7%
Tamoxifen, 7%
Anastrozole, 7%
Palbociclib + fulvestrant,
8%
Fulvestrant + letrozole, 6%
Chemotherapy (Eribulin),
6%
Fulvestrant + Anastrozole,
6%
Source: Novartis, data on file
Second-line Treatment
• 83% of patients received endocrine therapies and 17% of patients
received chemotherapy
• The duration of treatment for endocrine therapies and chemotherapy was
sourced from randomized controlled trials (RCTs) for the target population
(Novartis, data on file).4, 11-13
All chemotherapies in the analysis (represented
by eribulin) were assigned a 4.9-month treatment duration9
Third-line Treatment
• 39% of patients received endocrine therapies and 30% of patients
received chemotherapy, while 31% of patients received no treatment
(Novartis, data on file)
• The duration of treatment for endocrine therapies and chemotherapy was
sourced from RCTs for the target population.4,11-13
All chemotherapies were
assigned a 4.7-month treatment duration9
due to the absence of treatment
duration data in the third-line setting
Adverse Events
• Themodelincludedseriousadverseevents(AEs)(CTCAE(Common
terminologycriteriaforadverseevents)Grade≥3)reportedmorefrequently
withribociclib5
orpalbociclib3
versusplacebo(anemia,diarrhea,fatigue,
infection,nausea,febrileneutropenia,pulmonaryembolism,andvomiting)
andthat(frompreviousHTAsubmissionsandconsultationswithmodelling
experts)weredeemedrelevantandrelatedtotreatment,werelikelytoresult
inhospitalization,orhadameaningfulimpactonpatientwell-being
Cost Inputs
• Allcostswerein2016USdollarsinflatedusingtheConsumerPriceIndex(CPI)14
• The acquisition costs represented the lowest wholesale acquisition
cost (WAC) of each medication within Medi-Span Price Rx®
(Table 2)15
and allowed for patient co-payments. Eribulin was chosen to represent
first-line chemotherapy options because it was the highest cost first-line
chemotherapy
• A patient co-payment was applied to the monthly treatment acquisition
cost (Table 2)
• The cost of each AE was assumed to reflect an average hospitalization
related to that event (Table 2).16,17
The frequency of each AE for each
treatment was obtained from the literature3,5,11,13,18-21
• Monthly treatment administration costs were derived from the 2016
Medicare Physician Fee Schedule using Medicare facility prices ($179 for
fulvestrant and $771 for chemotherapy)22
• Monitoring costs included outpatient management, hospitalization,
laboratory monitoring, and imaging (PFS health state only), and palliative
care costs (progressed disease only) (total cost per month: $686 for PFS
and $6,199 for PD)14,23
• Monitoring costs also included monthly add-on monitoring costs (hepatic
enzymes, complete blood count, and ECG) for ribociclib and palbociclib
upon treatment initiation ($138.48 vs. $42.36) and regularly thereafter
($21.72 vs. $10.59)15,24,25
Table 2. Cost Inputs
Drug Dose (mg)
WAC cost/
month ($)
Copayment
($)
Adverse
event cost,
total ($)
Ribociclib
600.0 10,950 567
1,348.79400.0 8,760 567
200.0 4,380 567
Add-on letrozole 2.5 7 11
Palbociclib 125/100/75 10,963 567 1,734.76
Add-on letrozole 2.5 7 11
Letrozole
(monotherapy)
2.5 7 11 572.75
Fulvestrant 500.0 1,863 373 831.00
Add-on anastrozole 1.0 4 11
Fulvestrant 500.0 1,863 373
Exemestane 25.0 304 11 639.90
Tamoxifen 20.0 21 11 959.14
Anastrozole
(monotherapy)
1.0 4 11 572.75
Palbociclib 125/100/75 10,963 567 911.40
Add-on fulvestrant 500.0 1,863 373
Fulvestrant 500.0 1,863 373 789.36
Add-on letrozole 2.5 7 11
Chemotherapy
(eribulin)
1.23 4,200 827 1,026.78
Sources: 3, 5, 11, 13, 15-22
WAC, Wholesale acquisition cost
Deterministic Sensitivity Analysis (DSA)
• A one-way DSA was performed to assess the influence of key model input
parameters (acquisition cost, monitoring cost, first-line treatment duration,
progression-free health state costs, and post-progression health state
costs; ±10% variation) on budget impact
Results
• Out of 1,000,000 health plan members, 263 were post-menopausal
patients with HR+/HER2- advanced/metastatic breast cancer were
eligible for CDK 4/6 inhibitor therapy
• Within both scenarios, drug acquisition cost was the major component of
total cost (Table 3)
• The introduction of ribociclib resulted in $3.01M cumulative total savings
over three years, attributed to reduced costs (drug acquisition, $2.72M;
subsequent therapy, $96K; AEs, $82K) (Table 4)
• Savings per year increased over the time horizon with increased market
share of ribociclib: $125K, $1.04M, and $1.85M in Years 1–3, respectively
($0.01, $0.09, and $0.15 incremental cost savings per member per month,
respectively)
• The introduction of ribociclib resulted in a cost saving per treated patient
per month of $39.57 in Year 1, $327.73 in Year 2, and $525.28 in Year 3,
yielding a cumulative incremental cost saving of $318.11 per member
treated per month
• The key drivers of the net budget impact included the acquisition,
2+ months, of ribociclib, which resulted in a change of 31% (increase/
decrease) following a reduction/increase in the base case parameter.
Other drivers included the acquisition palbociclib + letrozole at 2+ months
(+/- 28%), treatment duration of ribociclib (-4%, -10%), and treatment
duration of palbociclib + letrozole (-28%, 17%) (Figure 2)
• The results were not sensitive to assumptions about the treatment
duration of ribociclib + letrozole, likely due to the magnitude of cost savings
achieved with the introduction of ribociclib into the marketplace
Table 3. Cumulative and Disaggregated Costs Both Scenarios
Cost ($)
Without ribociclib With ribociclib
Year
1
Year
2
Year
3
Cumu-
lative
Year
1
Year
2
Year
3
Cumu-
lative
Total drug acquisition
costs
18M 28M 31M 76M 17M 27M 29M 73M
Ribociclib +
letrozole
0K 0K 0K 0K 896K 4M 7M 12M
Palbociclib
+letrozole
13M 21M 22M 56M 12M 16M 14M 42M
Other comparators 4.65M 6.88M 8.22M 19.74M 4.65M 6.88M 7.87M 19.39M
Total drug
administration costs
107K 116K 110K 334K 107K 116K 109K 332K
Total drug monitoring
costs
10K 17K 19K 47K 12K 27K 36K 75K
Total disease
management costs/
non-drug medical
costs
3M 7M 7M 17M 3M 7M 7M 17M
Total adverse event
cost
303K 651K 1M 2M 299K 627K 953K 2M
Total subsequent
therapy costs
2M 8M 8M 18M 2M 8M 8M 18M
Second line 2M 6M 6M 14M 2M 6M 6M 14M
Third line 240K 2M 2M 4M 313K 2M 2M 4M
Total indirect costs 0K 0K 0k 0K 0K 0K 0K 0K
Total cost 23M 44M 47M 23M 43M 45M
Cumulative total
cost
23M 66M 113M 23M 65M 110M
Total costs per
member per month
1.90 3.64 3.90 1.89 3.55 3.74
1K, 1000; 1M, 1 million
Table 4. Incremental Cost Results for the Scenario with Ribociclib
versus the Scenario without Ribociclib
Incremental cost, $ (%)
Cost center Year 1 Year 2 Year 3 Cumulative
Drug acquisition -197K (-1.1) -943K (-3.5) -1575K (-5.4) -2716K (-3.7)
Drug administration 0 0 -1K (-1.0) -1K (-0.3)
Drug monitoring 2K (+16.4) 10K (+36.3) 16K (+45.4) 28K (+37.3)
Disease monitoring/non-drug
medical
0 -60K (-0.9) -85K (-1.2) -145K (-0.9)
Adverse events -3K (-1.1) -24K (-3.9) -54K (-5.7) -82K (-4.4)
Subsequent therapy 73K (+3.6) -19K (-0.2) -151K (-1.9) -96K (-0.5)
Second line 0 (0) 0 (0) 0 (0) 0 (0)
Third line 73K (+23.4) -19K (-1.1) -151K (-8.7) -96K (-2.5)
Total -125K -1036K -1850K -3012K
Total PMPM -0.01 -0.09 -0.15
Total PMTM -39.57 -327.73 -585.28
1K, 1000; PMPM, Per member per month; PMTM, Per member treated per month
Figure 2. Deterministic Sensitivity Analysis
-5000 -4000 -3000 -2000 -1000 0
Monitoring costs for Ribociclib
Health state costs, PFS
Health state costs, PPS
Acquisition, 1stmonth, Ribociclib
Acquisition, 1st month, Palbociclib + Letrozole
Acquisition, 2+months, Ribociclib
Treatment duration, Ribociclib
Treatment duration, Palbociclib + Letrozole
Acquisition, 2+ months, Palbociclib + Letrozole
$, Thousands
BI Low
BI High
Conclusions
• The introduction of ribociclib as a first-line treatment option for post-
menopausal women with HR+/HER2- advanced or metastatic
breast cancer in the US offers a cost-saving option with reduced
drug acquisition, adverse event, and subsequent treatment costs for
commercial payers
• Key drivers of the net budget impact include the acquisition cost of
palbociclib + letrozole, the acquisition cost of ribociclib + letrozole, and
the acquisition cost of palbociclib
Acknowledgements
Editorial support was provided by Lorena Tonarelli and by Nick Rusbridge
(PAREXEL)
References
1. Cardoso, F. Ann Oncol. 2017; 28:16-33.
2. Gradishar, W.J. J Natl Compr Canc Netw. 2016;
14:324-54.
3. Finn, R.S. Lancet Oncol. 2015; 16:25-35.
4. Finn, R.S. N Engl J Med. 2016; 375:1925-1936.
5. Hortobagyi, G.N. N Engl J Med. 2016; 375:1738-1748.
6. Rugo, H.S. J Oncol Pract. 2016; 12:583-7.
7. Howden, L.M., Meyer, J.A. 2010.
8. SEER, SEER Cancer Statistical Review, 1975-2013.
2016.
9. Xie, J. J Med Econ. 2013; 16:278-88.
10. Bachelot, T. J Clin Oncol. 2012; 30:2718-24.
11. Baselga, J. N Engl J Med. 2012; 366:520-9.
12. Ellis, M.J. J Clin Oncol. 2015; 33:3781-7.
13. Johnston, S.R. Lancet Oncol. 2013; 14:989-98.
14. U.S. Bureau of Labor Statistics. 2016.
15. Medispan Price Rx. [cited 2017; Available from:
https://pricerx.medispan.com/IngredientName.
aspx].
16. HCUP, N. HCUP NIS. 2013.
17. Michels, S.L. Pharmacoeconomics 2012; 30:809-23.
18. Finn, R.S. J Clin Oncol. 2016; 34:507.
19. Turner, N.C. N Engl J Med. 2015; 373:1672-3.
20. Cortes, J. Lancet 2011; 377:914-23.
21. Paridaens, R.J. J Clin Oncol. 2008; 26:4883-90.
22. Medicare. Medicare facility prices 2016.
23. Xie, J. Clin Breast Cancer 2015; 15:e263-76.
24. EMA. Ibrance (palbociclib). 2016.
25. Healthcare Bluebook. [cited 2017; Available from:
https://www.healthcarebluebook.com/].
Presented at the ISPOR 20th Annual European Congress, 4-8 November,
Glasgow, UK.
This study was funded by Novartis.
PCN62
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