BUDGET IMPACT ANALYSIS OF CDK4/6 INHIBITORS FOR THE FIRST LINE THERAPHY OF HR-POSITIVE HER2- NEGATIVE ADVANCED BREAST CANCER IN THE RUSSIAN FEDERATION Avxentyev N. A. 1 , Frolov M. Y. 2 , Pazukhina E. M. 3 1 Research Institute of Finance and Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia 2 Volgograd State Medical University of the Ministry of Health Russian Federation and Interregional Association of Clinical Pharmacologists, Volgograd, Russia 3 Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia PCN 81 ISPOR Europe 2018, Barcelona, Spain, 10-14 November, 2018 BACKGROUND ● Breast cancer is the most common malignant tumor and accounts for the most number of cancer-related deaths in Russian women [1]. ● Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors ribociclib and palbociclib, both in combination with aromatase inhibitors, are approved for the 1 st line treatment of postmenopausal women with HR-positive HER2-negative advanced breast cancer in Russia [2], however no CDK4/6 inhibitor is included in the Russian Vital and Essential Drug list (VEDL). OBJECTIVES ● The aim of the current study is to conduct budget impact analysis of ribociclib and palbociclib for the 1 st line treatment of HR-positive HER2-negative advanced breast cancer from the Russian healthcare system perspective. METHODS ● We proposed partitioned survival model of breast cancer progression on ribociclib + letrozole (hereafter referred to ribociclib) and palbociclib + letrozole (hereafter referred to palbociclib), which is depicted on figure 1. ● Overall and progression-free survival on ribociclib were modeled using Weibull approximation of MONALEESA-2 trial results [3]. Time to ribociclib discontinuation was modeled with distinct exponential distribution, because a number of patients stopped drug therapy prior to disease progression in MONALEESA-2 trial. ● Survival functions for palbociclib were obtained with proportional hazard model and results of matching-adjusted indirect comparison (MAIC) of ribociclib vs palbociclib (table 1). Due to lack of clinical data on time to palbociclib discontinuation in PALOMA-1 and 2 trials, we assumed that hazard ratio for time to discontinuation from ribociclib vs palbociclib equals corresponding hazard ratio for progression-free survival. Mean duration of treatment in the model was 21,9 and 20,2 months on ribociclib and palbociclib for five-year time horizon, respectively. ● Time horizon of the model was 5 years, as proposed by the Russian guidelines for pharmacoeconomic research. We considered costs that included: ● use of ribociclib or palbociclib ● 2 nd and 3 rd lines of drug therapy (most commonly used endocrine and chemotherapy schemes were considered) ● adverse events treatments ● inpatient care (surgery and radiotherapy) ● outpatient care (oncologist visits for treatment monitoring). ● We accounted for ribociclib dose modifications due to specific adverse reactions. Mean dose intensity of ribociclib was taken from the MONALEESA-2 trial for months 1 – 16, and was assumed to be constant afterwards. ● Palbociclib dose modifications were not considered, because of manufacturer flat-price policy: one-cycle costs of palbociclib are equal for each possible dose strength. Drug wastage costs of palbociclib were not accounted either. ● The estimated number of patients, who can annually start treatment with either ribociclib or palbociclib, was approximately 8 200 women (figure 2). Budget impact was defined as difference in costs of treatment of this patient flow with ribociclib or palbociclib during first three years after inclusion of any CDK4/6 inhibitor into VEDL. Figure 1. Partitioned survival model of breast cancer progression Figure 2. Number of patients, who can start treatment with CDK4/6 inhibitors each year *Forecast for 2019-21 based on national statistics on breast cancer incidence [1] **probabilities were estimated during interviews with local clinical experts Table 1. Effectiveness of ribociclib and palbociclib, Hazard ratio (95 % confidence interval) Ribociclib + letrozole vs placebo + letrozole (MONALEESA-2 trial results [3]) Palbociclib + letrozole vs placebo + letrozole (PALOMA-1 trial results [4] and meta-analysis of PALOMA-1 [4] and PALOMA-2 [5]) Ribociclib + letrozole vs palbociclib + letrozole (MAIC results [6]) Overall survival 0,746 (0,517–1,078) 0,813 (0,492–1,345) 0,839 (0,440–1,598) Progression-free survival 0,568 (0,457–0,704) 0,55 (0,45–0,69) 0,904 (0,644–1,268) Table 2. Average 5-year per patient costs, US$ Costs Ribociclib Palbociclib Difference (ribociclib – palbociclib) Progression-free 71 398,27 90 076,01 -18 677,76 1st line drug treatment (ribociclib / palbociclib) 70 824,66 89 568,89 -18 744,23 AEs 83,30 31,72 51,58 Inpatient care 49,25 49,25 0,00 Radiotherapy 177,36 177,36 0,00 Additional drug therapy 70,08 66,12 3,96 Outpatient care 193,61 182,67 10,94 Progressed 8 678,24 8 653,87 24,37 Subsequent lines of drug treatment 8 416,04 8 391,02 25,03 Radiotherapy 99,55 100,71 -1,14 Additional drug therapy 43,22 43,09 0,13 Outpatient care 119,41 119,06 0,35 Total 80 076,50 98 729,89 -18 653,39 Newly diagnosed III-IV st. breast cancer* ● 2019: 20 928 patients ● 2020: 21 070 patients ● 2021: 21 206 patients % HR+ HER2-: 65%** ● 2019: 13 603 patients ● 2020: 13 695 patients ● 2021: 13 784 patients % eligible for CDK4/6 inhibitors: 60%** ● 2019: 8 162 patients ● 2020: 8 217 patients ● 2021: 8 270 patients RESULTS ● Monthly medication costs of ribociclib were US$ 4,345 1 , which is 9 % less than for palbociclib (US$ 4,757). Despite similar (no statistically significant difference) progression-free and overall survival profile, 5-year total per patient costs on ribociclib were US$ 80,076, which were US$ 18,653 or 19 % less than for palbociclib (table 2). ● Lower costs on ribociclib were driven by less monthly medication costs and potential of cost reduction due to dose reduction. ● If 8 200 women start treatment with ribociclib annually, in 3 years healthcare budget will save US$ 322 million, compared to treatment with palbociclib. DISCUSSION ● Primary limitations of the study were the lack of head-to-head trials of ribociclib and palbociclib and lack of mature overall survival data for palbociclib in the PALOMA-2 study. ● A strength of this economic study was that it considered every CDK4/6 inhibitor available in Russia for the 1 st line treatment of HR-positive HER2-negative advanced breast cancer. CONCLUSIONS Ribociclib is a cost-saving technology that could be recommended for inclusion into VEDL in Russia. LITERATURE 1. Kaprin Andrey D., et al. “Oncological care for the population of Russia in 2016.” (in Russian). Moscow (2017) 2. State drug registry of the Ministry of Health of the Russian Federation (in Russian) URL: https://grls.rosminzdrav.ru/ Default.aspx 3. 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.” Annals of Oncology (2018). 4. Finn, Richard S., 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.” The lancet oncology 16.1 (2015): 25-35. 5. Finn, Richard S., et al. “Palbociclib and letrozole in advanced breast cancer.” New England Journal of Medicine 375.20 (2016): 1925-1936. 6. Tremblay, Gabriel, et al. “Matching-adjusted indirect treatment comparison of ribociclib and palbociclib in HR+, HER2− advanced breast cancer.” Cancer management and research 10 (2018): 1319. 1 Here and after 1 USD = 62.33 RUB as of June 2018 Copies of this poster are for personal use only and may not be reproduced without written permission of the authors