ISPOR Europe, 10–14 November 2018, Barcelona, Spain Pharmacoeconomic evaluation of enzalutamide for the treatment of post-chemotherapy patients with metastatic castration-resistant prostate cancer in Russia Nikolay A Avxentyev, 1 Elena V Derkach, 2 Alexander S Makarov 3 1 Research Institute of Finance and Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia; 2 National Center for Health Technology Assessment, Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia; 3 Interregional Association of Clinical Pharmacologists, Volgograd, Russia INTRODUCTION • Enzalutamide, abiraterone acetate plus prednisone (hereafter referred to as abiraterone) and cabazitaxel plus prednisone (hereafter referred to as cabazitaxel) are approved for the post-chemotherapy treatment of metastatic castration-resistant prostate cancer (mCRPC) in Russia. 1 • Currently, none of these treatments are included in the Government Drug Reimbursement Programme (GDRP), the federal programme that provides benefits for certain population groups (mainly people with disabilities), which limits accessibility to these established and effective therapies for patients with limited treatment options. OBJECTIVE • This pharmacoeconomic evaluation compared enzalutamide, abiraterone and cabazitaxel used in the second-line setting after chemotherapy in patients with mCRPC from the Russian healthcare system perspective. METHODS • We considered three mCRPC consecutive treatment options that could be used after progression on chemotherapy: – Enzalutamide cabazitaxel – Abiraterone cabazitaxel – Cabazitaxel abiraterone • For each treatment option, we proposed a Markov chain model of mCRPC progression ( Figure 1 ). Although most patients die within 2–3 years, we used the 5-year time horizon as proposed by the national guidelines for pharmacoeconomic research. • The model is based on clinical effectiveness data from the randomised controlled trials AFFIRM 2 (enzalutamide), COU-AA-301 3,4 (abiraterone) and TROPIC 5 (cabazitaxel), and indirect comparisons of considered drugs ( Table 1 ). • The model was used to calculate direct medical costs associated with considered options that include: – Second- and third-line medications (abiraterone, enzalutamide and cabazitaxel). – Drug administration. – Third and higher grades of adverse event treatments. – Treatments of bone metastases (zoledronic acid or denosumab). – Pain relief (morphine or tramadol). – Oncologist visits. – End-of-life palliative care. • Budget impact, cost-effectiveness and cost- utility analyses were conducted. To calculate the number of patients with mCRPC who are eligible for drug reimbursement from GDRP, we used Russian epidemiology data on prostate cancer prevalence and data on clinical effectiveness of using docetaxel in the first-line setting ( Figure 2 ). 8-11 RESULTS • Use of enzalutamide, abiraterone and cabazitaxel resulted in 1.04, 0.94 and 0.96 quality-adjusted life-years, respectively ( Table 2 ). • Monthly medication costs for enzalutamide were $2973 (1 US$ = 61.73 RUB as of June 2018) per patient; 15% less than for abiraterone and 49% less than for cabazitaxel. • Overall, 5-year total medical costs were $53,959, $53,975 and $71,836 per patient for enzalutamide, abiraterone and cabazitaxel, respectively ( Table 3 ). • The smaller difference in total medical costs resulted from longer progression-free survival on enzalutamide compared to abiraterone or cabazitaxel. • If included in GDRP, enzalutamide results in the lowest budget impact: $105.70 million, compared to $105.73 million for abiraterone and $140.72 million for cabazitaxel. REFERENCES 1. Ministry of Health of the Russian Federation. 2018. Available at: https://grls.rosminzdrav.ru/Default.aspx. 2. Scher HI et al. N Engl J Med 2012; 367: 1187-1197. 3. de Bono JS et al. N Engl J Med 2011; 364: 1995-2005. 4. Fizazi K et al. Lancet Oncol 2012; 13: 983-992. 5. de Bono JS et al. Lancet 2010; 376: 1147-1154. 6. National Institute for Health and Care Excellence. 2012. Available at: www.nice.org.uk/guidance/ta259. 7. Tan PS et al. Clin Med Insights Oncol 2014; 8: 29-36. 8. Kaprin AD et al. “Oncological care for the population of Russia in 2016” [in Russian]. 2017. Moscow Oncologic Research Institute, Moscow, Russia. 9. Kirby M et al. Int J Clin Pract 2011; 65: 1180-1192. 10. Tannock IF et al. N Engl J Med 2004; 351: 1502-1512. 11. Oxenoyt GK et al. “Healthcare in Russia in 2017” [in Russian]. 2017. Russian Federal Service of Statistics, Moscow, Russia. ACKNOWLEDGEMENTS This study was funded by Astellas Pharma Inc and Pfizer Inc, the co-developers of enzalutamide. Editorial assistance was provided by Jane Beck and Lauren Smith from Complete HealthVizion, funded by the study sponsors. Figure 1. Markov model Stable disease Progression Death Figure 2. Number of patients used for the budget impact analysis Living patients with prostate cancer diagnosed 5 years ago 8 77,485 patients With castration-resistant prostate cancer (10%) 9 7749 patients With metastatic process (84%) 9 6509 patients Survived after first-line docetaxel (85%) 10 5532 patients Eligible for drug reimbursement from GDRP (35%) 8,11 1959 patients GDRP=Government Drug Reimbursement Programme. PCN91 Table 1. Indirect comparison of considered drugs Drugs compared Overall survival, HR (95% CI) Modified progression-free survival,* HR (95% CI) Enzalutamide vs placebo 0.63 (0.53, 0.75) 2 0.46 (0.40, 0.53) Abiraterone vs placebo 0.74 (0.64, 0.86) 4 0.63 (0.55, 0.72) 6 Enzalutamide vs abiraterone 0.85 (0.68, 1.07) 0.73 (0.60, 0.89) Cabazitaxel vs mitoxantrone 0.70 (0.59, 0.83) 5 0.74 (0.64, 0.86) 5 Enzalutamide vs cabazitaxel † 0.90 (0.71, 1.15) 0.62 (0.51, 0.76) *We used a broad definition of progression for more accurate modelling of time to treatment discontinuation. Modified progression-free survival for enzalutamide was defined as the time to radiographic progression, first skeletal-related event or death, whichever occurs first, and was calculated using patient level data from the AFFIRM trial; for abiraterone, time to PSA progression, radiographic progression, increase in glucocorticoid use, pain progression, skeletal-related event, initiation of a new cancer therapy or death, whichever occurs first; for cabazitaxel, PSA progression, radiological progression, symptomatic progression or death, whichever occurs first (as in the TROPIC trial); in general, the currently used progression definition for enzalutamide was more restrictive, compared to abiraterone or cabazitaxel, which may systematically bias the indirect treatment comparison results in favour of enzalutamide. This should be treated as an important model limitation, however, our estimate was more conservative compared to indirect treatment comparison of enzalutamide versus abiraterone for radiographic progression: HR 0.61 (95% CI 0.50, 0.74) 7 ; † For indirect comparison of enzalutamide versus mitoxantrone, we assumed equal effectiveness of mitoxantrone and placebo; this was justified by the fact that in earlier studies mitoxantrone plus corticosteroid versus corticosteroid alone did not demonstrate survival benefit in the chemotherapy-naïve populations, hence it would be almost impossible that it could be beneficial in patients who progressed on chemotherapy. CI=confidence interval; HR=hazard ratio; PSA=prostate-specific antigen. Table 2. Clinical outcomes Second-line treatment Life-years gained Quality-adjusted life-years Enzalutamide 1.61 1.04 Abiraterone 1.47 0.94 Cabazitaxel 1.51 0.96 Table 3. Cost (US$ per patient)* Cost per second-line treatment option Enzalutamide Abiraterone Cabazitaxel Enzalutamide– abiraterone Enzalutamide– cabazitaxel Stable disease 32,628 30,082 44,933 2546 -12,305 Drugs 30,078 27,992 41,201 2086 -11,123 Drug administration 0 0 529 0 -529 Adverse event treatments 5 63 1415 -58 -1410 Oncologist visits 50 77 70 -27 -19 Treatments of bone metastases 2495 1950 1719 544 776 Progression 21,331 23,893 26,903 -2562 -5573 Drugs 14,584 16,665 19,470 -2081 -4886 Drug administration 187 214 0 -27 187 Adverse event treatment 537 614 47 -77 491 Oncologist visits 190 202 234 -12 -43 Treatments of bone metastases 2242 2382 2750 -140 -508 Pain relief 3558 3780 4364 -222 -806 End-of-life palliative care 31 36 39 -4 -8 Total 53,959 53,975 71,836 -16 -17,878 *1 US$ = 61.73 RUB as of June 2018. CONCLUSION • Based on the assumptions of the model, enzalutamide is cost effective compared to abiraterone and cabazitaxel, and requires the same or less additional budget expenditure in Russia.