Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Health Services Research
Published in: BMC Health Services Research 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

Cost-utility analysis of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer in the Philippines

Authors: Anne Julienne Genuino, Usa Chaikledkaew, Anna Melissa Guerrero, Thanyanan Reungwetwattana, Ammarin Thakkinstian

Published in: BMC Health Services Research | Issue 1/2019

Login to get access

Abstract

Background

Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions.

Methods

A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty.

Results

Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years.

Conclusion

At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness.
Literature
1.
2.
Laudico AVM-LM, Medina V, Mapua C, Valenzuela F, Pukkala E. Philippine cancer facts and estimates. Manila: Department of Health – Disease Prevention and Control Bureau; 2015.
3.
Wolff ACHM, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMed
4.
Gajria D, Chandarlapaty S. HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev Anticancer Ther. 2011;11(2):263–75.PubMedPubMedCentralCrossRef
5.
Kwan MLKL, Weltzien E, Maring B, Kutner SE, Fulton RS, Lee MM, Ambrosone CB, Caan BJ. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res. 2009;11(3):R31.PubMedPubMedCentralCrossRef
6.
Parise CABK, Brown MM, Caggiano V. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J. 2009;15(6):593–602.PubMedCrossRef
7.
Philippines DoH-NBCCP. National breast cancer control program - HER2 testing census. In: Bureau DoH-DPaC, editor. 2013.
8.
9.
Cameron DP-GM, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–205.PubMedPubMedCentralCrossRef
10.
Perez EARE, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N983. J Clin Oncol. 2014;23(31):7811–9.
11.
Romond EHJJ, Rastogi P, Swain SM, Geyer CE Jr, Ewer MS, Rathi V, Fehrenbacher L, Brufsky A, Azar CA, Flynn PJ, Zapas JL, Polikoff J, Gross HM, Biggs DD, Atkins JN, Tan-Chiu E, Zheng P, Yothers G, Mamounas EP, Wolmark N. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2–positive breast cancer. J Clin Oncol. 2012;30(31):3792–9.PubMedPubMedCentralCrossRef
12.
Advani PPBK, Dockter TJ, Colon-Otero G, Perez EA. Long term cardiac safety analysis of NCCTG N9831 (alliance) adjuvant trastuzumab trial. J Clin Oncol. 2016;34(6):581–7.PubMedCrossRef
13.
Slamon DEW, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.PubMedPubMedCentralCrossRef
14.
Joensuu HBP, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouacil, epirubicin and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009;27(34):5685–92.PubMedCrossRef
15.
Spielmann MRH, Delozier T, Canon JL, Romieu G, Bourgeois H, Extra JM, Serin D, Kerbrat P, Machiels JP, Lortholary A, Orfeuvre H, Campone M, Hardy-Bessard AC, Coudert B, Maerevoet M, Piot G, Kramar A, Martin AL, Penault-Llorca F. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009;27(36):6129–34.PubMedCrossRef
16.
Joensuu HK-LP, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Saarni O, Helle L, Villman K, Nyandoto P, Nilsson G, Leinonen M, Kataja V, Bono P, Lindman H. Outcome of patients with HER2-positive breast cancer treated with or without adjuvant trastuzumab in the Finland Capecitabine Trial (FinXX). Acta Oncol. 2014;53(2):186–94.PubMedCrossRef
17.
Senkus EKS, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S, Cardoso F. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8–30.CrossRefPubMed
18.
Network. NCC. Guidelines clinical practice guidelines in oncology- breast cancer version 2.2017. 2017.
19.
Force PSoMO-CPT. Clinical pathways for the medical management of the top 10 solid malignant tumors in the Philippines Philippine Society of Medical Oncology. 2015.
20.
Dedes KJST, Imesch P, Fedier A, Fehr MK, Fink D. Cost-effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a model-based analysis of the HERA and FinHer trial. Ann Oncol. 2007;18(9):1493–9.PubMedCrossRef
21.
Garrison LP Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer. 2007;110(3):489–98.PubMedCrossRef
22.
Kurian AWTR, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007;25(6):634–41.PubMedCrossRef
23.
Liberato NLMM, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2007;25(6):625–33.PubMedCrossRef
24.
Shiroiwa TFT, Shimozuma K, Ohashi Y, Tsutani K. The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data. Breast Cancer Res Treat. 2008;109(3):559–66.PubMedCrossRef
25.
Chen WJZ, Shao Z, Sun Q, Shen K. An economic evaluation of adjuvant trastuzumab therapy in HER2-positive early breast cancer. Value Health. 2009;12(Suppl 3):S82–4.PubMedCrossRef
26.
Skedgel CRD, Younis T. The cost-utility of sequential adjuvant trastuzumab in women with Her2/Neu-positive breast cancer: an analysis based on updated results from the HERA trial. Value Health. 2009;12(5):641–8.PubMedCrossRef
27.
Van Vlaenderen ICJ, Cocquyt V, Jerusalem G, Machiels JP, Neven P, Nechelput M, Delabaye I, Gyldmark M, Annemans L. Trastuzumab treatment of early stage breast cancer is cost-effective from the perspective of the Belgian health care authorities. Acta Clin Belg. 2009;64(2):100–12.PubMedCrossRef
28.
Macedo AMI, Andrade S, Cirrincione A, Ray J. Cost-effectiveness of trastuzumab in the treatment of early stages breast cancer patients, in Portugal. Acta Medica Port. 2010;23(3):475–82.
29.
Hall PSHC, McCabe C, Oluboyede Y, Round J, Cameron DA. Updated cost-effectiveness analysis of trastuzumab for early breast cancer: a UK perspective considering duration of benefit, long-term toxicity and pattern of recurrence. Pharmacoeconomics. 2011;29(5):415–32.PubMedCrossRef
30.
Hedden LORS, Lohrisch C, Chia S, Speers C, Kovacic L, Taylor S, Peacock S. Assessing the real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu positive breast cancer. Oncologist. 2012;17(2):164–71.PubMedPubMedCentralCrossRef
31.
Buendía JAVC, Pichón-Rivière A. An economic evaluation of trastuzumab as adjuvant treatment of early HER2-positive breast cancer patients in Colombia. Biomedica. 2013;33(3):411–7.PubMedCrossRef
32.
Pichon-Riviere AGO, Augustovski F, Vallejos C, Huayanay L, Bueno Mdel P, Rodriguez A, de Andrade CJ, Buendía JA, Drummond M. Implications of global pricing policies on access to innovative drugs: the case of trastuzumab in Seven Latin American Countries. Int J Technol Assess Health Care. 2015;31(1–2):2–11.PubMedCrossRef
33.
Aboutorabi AHM, Ghaderi H, Salehi M, Ghiasipour M. Cost-effectiveness analysis of trastuzumab in the adjuvant treatment for early breast cancer. Global J Health Sci. 2015;7(1):98–106.
34.
Lang HCCH, Chiou TJ, Chan AL. The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan. J Med Econ. 2016;19(10):923–7.PubMedCrossRef
35.
Leung WKG, Nair N, Blakely T. Adjuvant trastuzumab in HER2-positive early breast cancer by age and hormone receptor status: a cost-utility analysis. PLoS Med. 2016;13(8):e1002067.PubMedPubMedCentralCrossRef
36.
Society PC. DOH breast cancer medicine access program (BCMAP) follow-up data of non-trastuzumab HER2+ breast cancer patients. In: Society PC, editor. Manila; 2018.
37.
38.
Kongbutr R, Koontreer S, Traianat N, Vatakapan C. Economic evaluation of trastuzumab for treatment of breast cancer in Thailand; 2012.
39.
Pérez EARE, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–73.PubMedPubMedCentralCrossRef
40.
Genuino AJM, Chaikledkaew U, Ong DT, Reungwetwattana T, Thakkinstian A. Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis; 2018.
41.
Anh NQ N HV., Ha, N. T., Anh, N., Thuy, H., Hanh, N. T. M.,… Mendel, N. V. Assessment of the quality of life of breast and cervical cancer in Viet Nam in 2014. 2014.
42.
Group DBCCPGTW. Clinical practice guidelines for stages 0-IIIB breast cancer at first diagnosis. In: Division D-P, editor. 1 ed. 2014.
43.
Force PSoMO-CPT. Clinical pathways for the medical management of the top 10 solid malignant tumors in the Philippines 2015. Manila. 2015.
44.
Corporation PHI. PHIC circular 0035 s.2013 - implementing guidelines on medical and procedure case rates. Manila: Philippine Health Insurance Corporation; 2013.
45.
Wong JQ. Facility-based intervention costing for the 48 highest burden diseases in the guaranteed health benefits package of the Department of Health and the Philippine Health Insurance Corporation. In: Technology DoSa, editor. Department of Science and Technology - Philippine Council for Health Research and Development: Manila; 2018.
46.
Philippines DoH, editor. The Philippine drug price reference index 2017. In: Philippines DoH, editor. Manila: Department of Health Philippines; 2018.
47.
Division DHP-P. Breast cancer medicines access program procurement data 2011–2017. In: Division DoHP-P, editor; 2018.
48.
49.
Riewpaiboon A. Standard cost lists for health economic evaluation in Thailand. Med Assoc Thai. 2014;97(Suppl 5):S127.
50.
51.
52.
Dokainish HTK, Zhu J, Roy A, AlHabib KF, ElSayed A, Palileo-Villaneuva L, Lopez-Jaramillo P, Karaye K, Yusoff K, Orlandini A, Sliwa K, Mondo C, Lanas F, Prabhakaran D, Badr A, Elmaghawry M, Damasceno A, Tibazarwa K, Belley-Cote E, Balasubramanian K, Islam S, Yacoub MH, Huffman MD, Harkness K, Grinvalds A, McKelvie R, Bangdiwala SI, Yusuf S, INTER-CHF Investigators. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017;5(7):e665–72.PubMedCrossRef
53.
54.
55.
Division DP-P. Total spending for DOH BCMAP In: Division P, editor. Manila; 2018.
56.
Bureau DP-DPaC. Work and financial plan 2017 - breast cancer drugs. In: Bureau DPaC, editor. Manila. 2017.
Metadata
Title
Cost-utility analysis of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer in the Philippines
Authors
Anne Julienne Genuino
Usa Chaikledkaew
Anna Melissa Guerrero
Thanyanan Reungwetwattana
Ammarin Thakkinstian
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Health Services Research / Issue 1/2019
Electronic ISSN: 1472-6963
DOI
https://doi.org/10.1186/s12913-019-4715-8

Other articles of this Issue 1/2019

BMC Health Services Research 1/2019 Go to the issue

Research article

Are midwives in the Netherlands satisfied with their jobs? A systematic examination of satisfaction levels among hospital and primary-care midwives in the Netherlands

Research article

Mindset modification of community pharmacists in a collaborative relationship between a major hospital and neighboring community pharmacies: a qualitative study

Research article

Ethical problems in nursing management – a cross-sectional survey about solving problems

Research article

The effect of racial and gender concordance between physicians and patients on the assessment of hospitalist performance: a pilot study

Research article

The emotional labour of quality improvement work in end of life care: a qualitative study of Patient and Family Centred Care (PFCC) in England

Research article

An assessment of awareness of mental health conditions and its association with socio-demographic characteristics: a cross-sectional study in a rural district in Bangladesh