EE50
A cost-consequence model of using the 21-gene breast ® Recurrence Score assay to identify patients with early-stage node-positive (N1) breast cancer who benefit from adjuvant chemotherapy in the Netherlands (SUPPLEMENT) Peter M. Machielsen a; Felix E. de Jongh b; Pieter B. Drost c; Martijn J.H.G. Simons d; Jelle A. Spoorendonk a,
d
Exact Sciences, the Netherlands; b, Ikazia Ziekenhuis Rotterdam, the Netherlands; c, Exact Sciences, Baar, Switzerland; d, OPEN Health Group, Rotterdam, the Netherlands
Table 1. Costs for ACT, treating AEs, productivity losses and GEP testing
INTRODUCTION • Early-stage (I, II, IIIa), hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), 1-3 node positive (N1) breast cancer patients are often curatively treated with endocrine therapy (ET) and adjuvant chemotherapy (ACT) to reduce the chance of recurrences.
Cost category
Costs
Description
3 x FEC100 + 3xT
€5,016
Administered to 50% of the patient population.
4 x (dd)AC + 12xP (weekly)
€6,492
Administered to 25% of the patient population.
4 x (dd)AC + 4xT
€5,276
Administered to 25% of the patient population.
Acquisition costs ACT (average) 5
€5,450
An average cost for ACT acquisition was calculated based on the three most frequently administered treatment regimens in this patient population.
3 x FEC100 + 3xT
€4,200
Administered to 50% of the patient population.
4 x (dd)AC + 12xP (weekly)
€11,200
Administered to 25% of the patient population.
4 x (dd)AC + 4xT
€5,600
Administered to 25% of the patient population.
Administration costs ACT (average) 6
€6,300
An average cost for ACT administration was calculated based on the three most frequently administered treatment regimens in this patient population.
Short-term AEs grade I/II
€1,154*
• A validated cost-consequence model for node negative (N0) breast cancer patients2 was used as the basis to create the N1 model (Figure 1), which was revalidated by a clinical oncology expert specialized in breast cancer and by using external data.
Short-term AEs grade III
€2,071*
• The model compared the deterministic costs and consequences of two diagnostic strategies, ‘21-gene breast RS®’ and ‘no GEP testing’, and the subsequent ACT use.
Short-term AEs grade IV
€299*
Long-term AEs (AML)
€347
• Based on an incidence of 15,000 breast cancer patients, N=821 patients were eligible for the 21-gene breast RS® assay in the Netherlands (Figure 2).3,4
Long-term AEs (CHF)
€188
• In the ‘21-gene breast RS®’ strategy, patients were stratified into two risk groups based on RS®, with only the high-risk group receiving ACT (Figure 1). All patients in the ‘no GEP testing’ strategy were treated with ACT.
Productivity losses 18,19
• Each diagnostic strategy included costs for: acquisition and administration of ACT, treatment of adverse events (AEs), productivity losses, and GEP testing, according to RS® results (Table 1). Costs for ET and treating recurrences were not included as they were equal in both testing strategies.
GEP testing
• However, not all women, e.g., post-menopausal women, benefit from ACT and can be overtreated leading to considerable humanistic and economic burden.1 • Randomised controlled studies have demonstrated that the 21-gene Breast Recurrence Score (RS)® assay can identify patients at higher risk for disease recurrence and predict the benefit of ACT.1 • The budgetary consequence of using the 21-gene breast RS® assay versus no gene expression profiling (GEP) testing for N1 patients in the Netherlands is currently unknown.
OBJECTIVE RS®
• To assess the expected budgetary consequences of introducing the 21-gene breast assay, to identify patients with a high-risk RS® result who will benefit from ACT in postmenopausal women with early-stage, HR+, HER2-, N1 invasive breast cancer, in the Dutch clinical practice.
METHODS
• The model’s time horizon was 5 years, a societal Dutch healthcare perspective was adopted, and the data was derived from the literature. • Costs were calculated per cost category, as total for the entire population and per patient, for each diagnostic strategy.
20
No GEP testing
Neutropenia, fatigue, dyspnoea and skin rashes amongst others. The probability of patients experiencing these AEs was multiplied with the costs for treating them.9-17 AML & CHF. The 5-yeas probability of patients experiencing these AEs was multiplied with the costs for treating them.
€3,638
The friction method was used. Assumptions: average sick leave of 24 weeks, post-menopausal women worked until 65 year, and for 20 hours a week on average.
€4,594
Cost for using the 21-gene breast RS assay as a diagnostic test.
€0
There were no testing costs in the no GEP testing strategy.
*, Weighted average of the cost for treating multiple AEs based on the probability of occurrence. 3xFEC100+3xT, three cycles of fluorouracil-epirubicin-cyclophosphamide followed by three cycles of docetaxel. 4x(dd)AC+12xP(weekly), four cycles of doxorubicin-cyclophosphamide followed by twelve cycles of paclitaxel. 4x(dd)AC+4xT, four cycles of doxorubicin-cyclophosphamide followed by four cycles of docetaxel. ACT, adjuvant chemotherapy; AEs, adverse events; AML, Acute myeloid leukaemia; CHF, chronic heart failure; GEP, gene expression profiling; RS, recurrence score.
Figure 1. Structural overview of the cost-consequence model
Costs for ACT are calculated over a period of 6 months. ACT, Adjuvant Chemotherapy; GEP, gene expression profiling; HER2-, Human epidermal growth factor receptor 2 negative; HR+, Hormone receptor positive; N1, Nodal stage (1 to 3 positive lymph nodes); RS, Recurrence score.
Figure 2. Model population, eligible for 21-gene breast RS® Total population of patients with early-stage invasive breast cancer in the Netherlands (n=15,000)
Early-stage invasive breast cancer patients with stage I, II, IIIa disease (n=11,250)
Stage I, II, IIIa breast cancer patients who are HR+ and HER2- (n=8,269)
HR+, HER2-, stage I, II, IIIa breast cancer patients with 1-3 positive lymph nodes (N1) (n=1,216)
Post-menopausal women with early-stage, HR+, HER2-, N1 invasive breast cancer (n=821) HER2-, Human epidermal growth factor receptor 2 negative; HR+, Hormone receptor positive; N1, Nodal stage (1 to 3 positive lymph nodes).
ISPOR Europe 2022 - Vienna
EXS13789_1022_NL_NL
EE50
A cost-consequence model of using the 21-gene breast ® Recurrence Score assay to identify patients with early-stage node-positive (N1) breast cancer who benefit from adjuvant chemotherapy in the Netherlands (SUPPLEMENT) Peter M. Machielsen a; Felix E. de Jongh b; Pieter B. Drost c; Martijn J.H.G. Simons d; Jelle A. Spoorendonk a,
d
Exact Sciences, the Netherlands; b, Ikazia Ziekenhuis Rotterdam, the Netherlands; c, Exact Sciences, Baar, Switzerland; d, OPEN Health Group, Rotterdam, the Netherlands
RESULTS
CONCLUSIONS
• The main results are displayed in Figure 3.
• The initial costs for using the 21-gene breast RS® assay as a GEP test in N1 breast cancer patients amount €3.8 million but saves €10.8 million in chemotherapy costs and €2.5 million in productivity losses, compared to no GEP testing.
• Using the 21-gene breast RS® assay resulted in mean cost-savings of €11,528 per patient and €9.5 million over 6 months for the Dutch healthcare system when compared to no GEP testing. • The 21-gene breast RS® assay resulted in fewer patients receiving ACT and fewer AEs, sick days, and hospitalisations, which lead to cost-savings of €13.3 million compared to no GEP testing. • ACT was mainly responsible for driving up the costs.
• Using the 21-gene breast RS® assay as a diagnostic strategy in post-menopausal N1 breast cancer patients results in overall cost-savings of €9.5 million compared to no GEP testing. • Implementing the 21-gene breast RS® assay in this population can prevent overtreatment, which leads to less clinical and economic burden on the patient and Dutch healthcare system.
Figure 2. Results on the costs per category and total costs for the entire population (HR+, HER2-, N1) over 5 years
ACT, adjuvant chemotherapy; AE, adverse events; GEP, gene expression profiling.
REFERENCES 1. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021;385(25):2336-47. 2. de Jongh FE, Efe R, Herrmann KH, Spoorendonk JA. Cost and clinical benefits associated with Oncotype DX® test in patients with early-stage HR+/HER2- nodenegative breast cancer in the Netherlands. International Journal of Breast Cancer. 2022;2022:12. 3. DICA. NBCA jaarverslag 2020; 4. IKNL. NKR-cijfers. Available from: https://iknl.nl/nkr-cijfers. 5. Z-index. 2021; 6. NZA. DBC-zorgproduct 020107034 2021. Available from: https://www.opendisdata.nl/msz/zorgproduct/020107034; 7. Retèl VP, Byng D, Linn SC, Jóźwiak K, Koffijberg H, Rutgers EJ, et al. Cost-effectiveness analysis of the 70-gene signature compared with clinical assessment in breast cancer based on a randomised controlled trial. Eur J Cancer. 2020;137:193-203;
8. IKNL-NABON. Borstkanker. Landelijke richtlijn. Version 2.0. 2020; 9. Bouwmans C, Janssen J, Huijgens P, Uyl-de Groot C. Costs of haematological adverse events in chronic myeloid leukaemia patients: a retrospective cost analysis of the treatment of anaemia, neutropenia and thrombocytopenia in patients with chronic myeloid leukaemia. J Med Econ. 2009;12(2):164-9; 10.Wehler E, Zhao Z, Pinar Bilir S, Munakata J, Barber B. Economic burden of toxicities associated with treating metastatic melanoma in eight countries. Eur J Health Econ. 2017;18(1):49-58; 11.Zorginstituut Nederland. Pakketadvies palbociclib (Ibrance®), 11 april 2017; 12.De Jong LA, Gout-Zwart JJ, van den Bosch M, Koops M, Postma MJ. Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands: a real-world data based cost-effectiveness analysis. J Med Econ. 2019;22(4):306-18; 13.Van den Hurk CJ, van den Akker-van Marle ME, Breed WP, van de Poll-Franse LV, Nortier JW, Coebergh JW. Cost-effectiveness analysis of scalp cooling to reduce chemotherapy-induced alopecia. Acta Oncol. 2014;53(1):80-7; 14.Leunis A, Blommestein HM, Huijgens PC, Blijlevens NM, Jongen-Lavrencic M, Uyl-de Groot CA. The costs of initial treatment for patients with acute myeloid leukemia in the Netherlands. Leuk Res. 2013;37(3):245-50; 15.Zorginstituut Nederland. Herbeoordeling trastuzumab (Herceptin) bij HER2-positieve vroege borstkanker (2014); 16.Boekel NB, Jacobse JN, Schaapveld M, Hooning MJ, Gietema JA, Duane FK, et al. Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer. Br J Cancer. 2018;119(4):408-18; 17.Wolff AC, Blackford AL, Visvanathan K, Rugo HS, Moy B, Goldstein LJ, et al. Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience. J Clin Oncol. 2015;33(4):340-8; 18.Hakkaart-van Roijen L, Van der Linden N, Bouwmans C, Kanters T, SS T. Kostenhandleiding: Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg (ZIN). 2015; 19.CBS. StatLine. 2022; 20.NZa code 050531 - https://zorgproducten.nza.nl/ZoekZorgproduct.aspx?psId=14&pId=22973.
ACKNOWLEDGMENTS, DISCLOSURES and CONTACT The authors thank dr. Tim Jacobs from Exact Sciences and Tim Ignacio from OPEN Health Group for supervising and critically reviewing the presented work. ©2022 Genomic Health, Inc. All rights reserved. Oncotype DX, Oncotype DX Breast Recurrence Score, Recurrence Score and RS are trademarks or registered trademarks of Genomic Health, Inc., a wholly owned subsidiary of Exact Sciences Corporation. Exact Sciences is a registered trademark of Exact Sciences Corporation. Exact Sciences is a registered trademark of Exact Sciences Corporation. This presentation is the intellectual property of the authors. Contact Tim Ignacio (TimIgnacio@openhealthgroup.com) for permission to reprint and/or distribute.
ISPOR Europe 2022 - Vienna
EXS13789_1022_NL_NL