PHARMACOECONOMIC EVALUATION OF RIBOCICLIB FOR THE FIRST-LINE TREATMENT OF HR-POSITIVE HER2-NEGATIVE ADVANCED BREAST CANCER

Background. Breast cancer is the most common malignant tumor and accounts for the most number of cancer-related deaths among Russian women. Combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor ribociclib and aromatase inhibitor is approved for the first-line treatment of postmenopausal women with HR-positive HER2-negative advanced breast cancer.

Objective: to conduct pharmacoeconomic evaluation of using ribociclib + aromatase inhibitor for the first-line treatment of HR-positive HER2- negative advanced breast cancer from the Russian healthcare system perspective.

Materials and methods. The comparator was palbociclib + aromatase inhibitor, because ribociclib and palbociclib have similar mechanism of action and are the only available CDK4/6 inhibitors that could be used for treatment of HR-positive HER2-negative advanced breast cancer in Russia. Using clinical trials data and published results of matching adjusted indirect comparison (MAIC), we proposed Markov chain model of breast cancer progression and estimated direct medical costs associated with two considered options (first and subsequent lines of drug therapy, adverse events treatment, inpatient and outpatient care). Budget impact and cost-effectiveness analyses were conducted. Mean duration of treatment in the model was 21,9 and 20,2 months on ribociclib and palbociclib for five year time horizon respectively.

Results and conclusion. Monthly medication costs of ribociclib (270 814.18 RUB) were 9 % less than for palbociclib (296 517.21 RUB). Driven by less monthly medication costs and potential of cost reduction due to dose reduction, five-year total medical per patient costs for ribociclib were 4 991 168 RUB, which were 1 162 666 RUB or 19 % less than for palbociclib. Ribociclib also had better (lower) cost/effectiveness ratio (1 244 906 vs 1 595 867 RUB per life year). As the result, ribociclib was considered a cost-saving option. If 8 162–8 270 women receive ribociclib, public healthcare expenditures will decrease by 20.1 billion RUB (21 %) within 3 years, compared to palbociclib.

1. Злокачественные новообразования в России в 2016 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2017. 250 с. [Malignant tumors in Russia in 2016 (incidence and mortality). Eds.: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: P. Herzen Moscow Oncology Research Institute – a branch of the National Medical Research Radiology Center, Ministry of Health of Russia, 2017. 250 p. (In Russ.)].

2. Клинические рекомендации Минздрава России. Рак молочной железы. Доступно по: http://cr.rosminzdrav.ru/schema. html?id=236#/text. [Clinical guidelines of the Ministry of Health of Russia. Breast cancer. Available at: http://cr.rosminzdrav. ru/schema. html?id=236#/text. (In Russ.)].

3. Клинические рекомендации РООМ по лечению метастатического рака молочной железы. Общероссийская общественная организация «Российское общество онкомамологов», 2014 г. Доступно по: http://www.breastcancersociety.ru/rek/view/29. [Clinical guidelines of the Russian Society of Oncomamologists on the treatment of metastatic breast cancer. Russian public organization “Russian Society of Oncomamologists”, 2014. Available at: http://www.breastcancersociety.ru/rek/view/29. (In Russ.)].

4. Клинические рекомендации по диагностике и лечению больных раком молочной железы. Ассоциация онкологов России, Москва, 2014 г. Доступно по: http://oncology-association.ru/docs/ recomend/may2015/24vz-rek.pdf. [Clinical guidelines for the diagnosis and treatment of breast cancer. Russian Association of Oncologists, Moscow, 2014. Available at: http://oncology-association. ru/docs/recomend/may2015/24vz-rek. pdf. (In Russ.)].

5. Государственный реестр лекарственных средств (ГРЛС). Доступно по: http:// grls.rosminzdrav.ru/GRLS. aspx. [State Register of Medicines(SRM). Available at: http://grls.rosminzdrav.ru/GRLS. aspx. (In Russ.)].

6. Распоряжение Правительства РФ от 23 октября 2017 г. № 2323-р «Об утверждении перечня жизненно необходимых и важнейших лекарственных препаратов для медицинского применения на 2018 год». [Decree of the Russian Federation Government No. 2323-r dated October 23, 2017 “On the approval of the list of vital and essential drugs for 2018”. (In Russ.)].

7. Плавинский С.Л., Шабалкин П.И. Использование ингибитора циклин-зависимых киназ 4/6(палбоциклиб) в терапии гормон-зависимого метастатического рака молочной железы. Анализ затраты – последствия. Сибирский онкологический журнал 2017;4(16):19–25. [Plavinskiy S.L., Shabalkin P.I. Cyclindependent kinase 4/6 inhibitor (palbociclib) in the treatment of hormonedependent metastatic breast cancer. Cost – impact analysis. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology 2017;4(16):19–25. (In Russ.)].

8. Hortobagyi G.N., Stemmer S.M., Burris H.A. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016;375(18):1738–48. PMID: 27717303. DOI: 10.1056/NEJMoa1609709.

9. Sonke G.S., Hart L.L., Campone M. et al. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptorpositive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat 2018;167(3):659–69. PMID: 29058175. DOI: 10.1007/s10549-017-4523-y.

10. O’Shaughnessy J., Petrakova K., Sonke G.S. et al. Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2-advanced breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat 2018;168(1):127–34. PMID: 29164421. DOI: 10.1007/s10549-017-4518-8.

11. Hortobagyi G.N. et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 2018 Apr 27. PMID: 29718092. DOI: 10.1093/annonc/mdy155.

12. Tremblay G., Chandiwana D., Dolph M. et al. Matching-adjusted indirect treatment comparison of ribociclib and palbociclib in HR+, HER2-advanced breast cancer. Cancer Manag Res 2018:10:1319–27. PMID: 29861642. DOI: 10.2147/CMAR.S163478.

13. Finn R.S., Crown J.P., Lang I. et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015;16(1):25–35. PMID: 25524798. DOI: 10.1016/S1470-2045(14)71159-3.

14. Finn R.S., Martin M., Rugo H.S. et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016;375(20):1925–36. DOI: 10.1056/NEJMoa1607303.

15. Данные о предельных размерах оптовых надбавок и предельных размерах розничных надбавок к ценам на жизненно необходимые и важнейшие лекарственные препараты, установленные в субъектах российской федерации (данные за 4 квартал 2017 г.) Доступно по: https://fas.gov.ru/documents/605937. [Information on the maximum wholesale and retail allowances for vital and essential medicines in the regions of the Russian Federation (as of Q4 2017). Available at: https://fas.gov.ru/documents/605937. (In Russ.)].

16. Saad E.D., Katz A., Buyse M. Overall survival and post-progression survival in advanced breast cancer: a review of recent randomized clinical trials. J Clin Oncol 2010;28(11):1958–62. PMID: 20194852. DOI: 10.1200/JCO. 2009.25.5414.

17. Постановление Правительства РФ от 8 декабря 2017 г. № 1492 «О Программе государственных гарантий бесплатного оказания гражданам медицинской помощи на 2018 год и на плановый период 2019 и 2020 годов». [Decree of the Russian Federation Government No. 1492 dated December 8, 2017 “On the Programme of state guarantees for free medical care for Russian citizens in 2018 and planning periods of 2019 and 2020”. (In Russ.)].

18. Письмо Министерства здравоохранения Российской Федерации № 11–7/ 10/2–8080 от 21 ноября 2017 года «О методических рекомендациях по способам оплаты медицинской помощи за счет средств обязательного медицинского страхования». [Letter of the Ministry of Health of Russia No. 11–7/10/2–8080 dated November 21, 2017 “Methodical recommendations on options of paying for medical care using the funds of compulsory medical insurance”. (In Russ.)].

19. Постановление Правительства РФ от 28.08.2014 № 871(ред. от 12.06.2017) «Об утверждении Правил формирования перечней лекарственных препаратов для медицинского применения и минимального ассортимента лекарственных препаратов, необходимых для оказания медицинской помощи». [Decree of the Russian Federation Government No. 871 dated August 28, 2014(rev. as of June 12, 2017) “On the approval of Rules for forming the lists of medicines and the minimum assortment of medicines necessary for providing medical care». (In Russ.)].