The pharmacoeconomic analysis of olaparib (Linparza®) application for the supporting therapy of patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer
Keywords:pharmacoeconomics, ovarian cancer, PARP-inhibitors, olaparib, Linparsa®
Among women, one of the common localizations of malignant tumors is ovarian cancer (OC). Two genes have been identified, and their mutations lead to hereditary forms of breast and ovarian cancer – BRCA1 and BRCA2. Women with BRCA-associated OC respond better to targeted drugs and have better survival rates against specific treatments. Targeted drugs for the treatment of BRCA-mutated OC are specific inhibitors of enzymes of the group poly- (ADP-ribose) polymerase (PARP). Currently, the only PARP inhibitor registered in Ukraine is olaparib (Linparza® drug, AstraZeneca, United Kingdom).
Aim. To assess the economic feasibility of the targeted olaparib therapy (Linparza® drug) for patients with BRCA mutated platinum-sensitive recurrent ovarian cancer (BRCA-MPS ROC) from the standpoint of the Ukrainian healthcare system.
Materials and methods. Determination of treatment outcomes and associated costs was performed using Markov analytical modeling based on the results of a randomized multicenter, open-label phase II clinical trial D0810C0019-Study 19. The model time horizon is 15 years. Clinical efficacy and safety of olaparib and placebo (WW strategy) were compared as the supportive therapy for patients with BRCA-MPS ROC. Based on the results of Markov simulation the methods of “cost-effectiveness” and “cost-utility” were used. Years of the saved life (LYG) were used as a criterion of efficiency. The QALY index was used as a criterion of utility. The cost of direct medical expenses, which structure was determined in accordance with the current Protocol, was taken into account. The cost of medical treatment was determined according to the register of the Ministry of Health of Ukraine as of 7.08.2019. The cost of medical services was determined according to the available price lists. The cost of correction of side effects of the chemotherapy was also considered. Discounting was determined at the level of 5 % annually. The sensitivity analysis of the results was performed on the price and dose of olaparib and the observation horizon.
Results. According to the simulation, the average life expectancy of patients with BRCA mutated platinum-sensitive recurrent ovarian cancer when using olaparib (Linparza® drug) as a supportive antitumor therapy is 4.8 LYG compared to 2.56 LYG in the WW strategy group. The olaparib supportive care strategy provides the patient with 3.61 years of quality of life compared to 1.87 years in the WW group. Thus, the use of olaparib provides the patient with an additional 2.24 years of life and 1.74 additional QALY. The total costs for the simulated period in the group of olaparib averaged 1893410.7 UAH, and in the WW group – 47466.9 UAH. The incremental coefficients of ICER (cost of 1 additional year of life) and ICUR (cost of 1 additional year of quality life) amounted to 824564,4 UAH, and 1063162.2 UAH, respectively.Conclusions. The pharmacoeconomic analysis based on Markov modeling and cost-effectiveness and cost-utility calculations has shown that olaparib (Linparza® drug) is highly effective in the treatment of BRCA-mutated platinum-sensitive recurrent ovarian cancer; it almost doubles the patients’ survival without recurrence. At the same time, olaparib is an expensive drug. The transition of half of the patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer from the “watch-and-wait” strategy to the treatment with olaparib requires an additional annual cost of 10,548,250.3 UAH.
Rybin, A. I. (2018). Optymizatsiia medykamentoznoho likuvannia khvorykh na rak yaiechnykiv: medyko-biolohichni osnovy prohnozuvannia ta podolannia platyno rezystentnosti. Doctor’s thesis. Kyiv, 354. http://unci.org.ua/wp-content/uploads/2014/11/dis-Рибін-А.І.pdf
Tsentr medychnoi statystyky MOZ Ukrainy. (n.d.). Avaialble at: http://medstat.gov.ua/ukr/statdan.html
Ferla, R., Calò, V., Cascio, S., Rinaldi, G., Badalamenti, G., Carreca, I., … Russo, A. (2007). Founder mutations in BRCA1 and BRCA2 genes. Annals of Oncology, 18, vi93–vi98. https://doi.org/10.1093/annonc/mdm234
Mamarasulova, D. Z., Mamadaliyeva, Ya. S., Ergashev, Z. A., Azizov,Yu. D. (2016). Otcenka geneticheskogo riska razvitiia raka iaichnika — mutatcii genov BRCA1 i BRCA2 v Andizhanskoi oblasti. Klinicheskaia onkologiia, 2, 37–39.
Bolton, K., Chenevix-Trench, G., Goh, C.,Sadetzki, S., Ramus, S., Pharoah, P. (2012). Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA, 307, 382–390. https://doi.org/10.1001/jama.2012.20
Khokhlova, S. V., Shilkina, A. A. (2017). PARP-ingibitory pri rake iaichnikov: profil toksichnosti. Meditsinskiy sovet, 6, 22–29.
Sultan, A., Swarup, S., Zaw, M., Han, M. M., Myat, Y. M., Aung, H. H., … Thein, K. Z. (2018). A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of hematological toxicities in patients with cancer treated with poly adenosine diphosphate ribose polymerase (PARP) inhibitors. Journal of Clinical Oncology, 36(34_suppl), 217–217. https://doi.org/10.1200/JCO.2018.36.34_suppl.217
Ma, J., Deng, H., Li, J., Hu, S., Yang, Y., Liu, S., Han, X. (2019). Efficacy and safety of olaparib of maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials. Cancer Management and Research, 11, 3061–3078. https://doi.org/10.2147/CMAR.S191107
Wiggans, A. J., Cass, G. K., Bryant, A., Lawrie, T. A., & Morrison, J. (2015). Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD007929.pub3
Guo, X. X., Wu, H. L., Shi, H. Y., Su, L., & Zhang, X. (2018). The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials. Cancer Management and Research, 10, 2553–2562. https://doi.org/10.2147/CMAR.S169558
Torres Toala, F., Solorzano, J., Baldi, J., Landaverde, D., & González, I. (2018). Budget Impact Analysis For Olaparib Maintenance Therapy for Brca-Mutated Platinum Sensitive Recurrent Ovarian Cancer in Costa Rica. Value in Health, 21, 1–268. https://doi.org/10.1016/j.jval.2018.04.127
Delgado-Ortega, L., Rubió, J., Garcías de España, M. (2018). Economic impact of olaparib on maintenance treatment of patients with BRCA-mutation positive, platinum-sensitive relapsing high-grade serous epithelial ovarian cancer in Spain. Farmacia Hospitalaria, 42(3), 95–102. https://doi.org/10.7399/fh.10904
Kerivna nastanova iz otsinky tekhnolohii okhorony zdorov’ia. (2018). Kyiv: MOZ Ukrainy, 54.
Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., … Matulonis, U. (2014). Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. The Lancet Oncology, 15(8), 852–861. https://doi.org/10.1016/S1470-2045(14)70228-1
National Institute for Health and Care Excellence. Final appraisal determination. (2015). Olaparib for maintenance treatment of relapsed, platinum-sensitive, BRCA mutation-positive ovarian, fallopian tube and peritoneal cancer following response to second-line or subsequent platinum-based chemotherapy, 61. Available at: https://www.nice.org.uk/guidance/ta381/documents/final-appraisal-determination-document
Ledermann, J. A., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., … Matulonis, U. (2016). Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. The Lancet Oncology, 17(11), 1579–1589. https://doi.org/10.1016/S1470-2045(16)30376-X
Cleary, J., Ddungu, H., Distelhorst, S. R., Ripamonti, C., Rodin, G. M., Bushnaq, M. A., … Anderson, B. O. (2013). Supportive and palliative care for metastatic breast cancer: Resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement. The Breast, 22(5), 616–627. https://doi.org/10.1016/j.breast.2013.07.052
Nakaz MOZU № 554 vid 17.09.2007. (2007). «Pro zatverdzhennia protokoliv nadannia medychnoi dopomohy za spetsialnistiu «onkolohiia». Available at: http://search.ligazakon.ua/l_doc2.nsf/link1/MOZ7355.html
Ledermann, J. A., & Pujade-Lauraine, E. (2019). Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer. Therapeutic Advances in Medical Oncology, 11, 1–18. https://doi.org/10.1177/1758835919849753
Derzhavnyi reiestr likarskykh zasobiv Ukrainy. (n.d.). Avaialble at: https://moz.gov.ua/derzhavnij-reestr-likarskih-zasobiv-ukraini
Zadeklarovani optovo-vidpuskni tsiny stanom na 01.08.2019. (2019). Avaialble at: http://moz.gov.ua/docfiles/Reestr
Preiskurant na meditcinskie uslugi. (n.d.). Available at: https://oncohelpclinic.com/poslugi/
Yakovleva, L.V. (Ed.). (2009). Farmakoekonomika : navchalnyi posibnyk dlia studentiv vyshchykh navchalnykh zakladiv. Vinnitsa: Novaya kniga, 208.
Paliychuk, O. V., Rossokha, Z. I., Galkin, F., Paliyschuk, L. Z. (2015). Otsinka asotsiatsii kliniko-patolohichnykh osoblyvostei pukhlynnoho protsesu z rezultatamy kliniko-henealohichnoho obstezhennia khvorykh na rak yaiechnyka ta hrudnoi zalozy – nosiiv mutatsii 538insC u heni BRCA1. Klinicheskaya onkologiya, 4(20).
Moore, K., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Friedlander, M., … DiSilvestro, P. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379(26), 2495–2505. https://doi.org/10.1056/NEJMoa1810858
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