Budget impact analysis of enzalutamide for the treatment of hormone-sensitive metastatic prostate cancer in Italy





Budget impact analysis, Economic evaluation, Enzalutamide, Italy, Prostate cancer


Backgroud: After demonstrating additional benefit versus standard of care in ARCHES and ENZAMET studies, enzalutamide was reimbursed in Italy in May 2022 by the National Health Service (NHS) for the treatment of hormone-sensitive metastatic prostate cancer (mHSPC).

Objective: This study estimates the financial impact associated to the introduction of enzalutamide for patients with mHSPC.

Methods: A budget impact model was developed with a dynamic cost calculator approach, in which the impact on subsequent lines of therapy was considered. The analysis considered the NHS perspective and a 3-year time horizon. Included costs were related to drug acquisition and administration, monitoring, patient follow-up and adverse events. Eligible population was estimated based on published literature, real-world data and experts’ opinion while market shares were assessed considering real-world data and assumptions. National tariffs and published literature were considered for unit costs.

Results: Eligible population was estimated at 6,200, 6,206 and 6,212 in years 1, 2 and 3 respectively. The introduction of enzalutamide, considering a progressive increase of market shares of 10%, 18% and 25%, is expected to overall increase NHS healthcare expenditure by € 688 thousands and € 2.6 and € 5.6 million in years 1, 2 and 3 respectively, corresponding on average to 1.55% of the overall prostate cancer expenditure.

Results are robust across one-way sensitivity analyses, while confidential discount agreements of on-patent drugs might significantly impact the estimates.

Conclusion: The introduction of enzalutamide for the treatment of adult patients with mHSPC is expected to increase patients’ health with a moderate impact on costs for the Italian NHS.


AIOM: Linee guida del Carcinoma della Prostata. 2021. Online https://snlg.iss.it/wp-content/uploads/2021/11/LG450-AIOM_Ca_prostata.pdf (Accessed October 2022)

AIRTUM: I numeri del cancro in Italia. 2020. https://www.epicentro.iss.it/tumori/pdf/2020_Numeri_Cancro-pazienti-web.pdf (Accessed October 2022)

Scher HI, Heller G. Clinical states in prostate cancer: toward a dynamic model of disease progression. Urology. 2000;55(3):323-327. https://doi.org/10.1016/S0090-4295(99)00471-9PMID:10699601 DOI: https://doi.org/10.1016/S0090-4295(99)00471-9

Anantharaman A, Small EJ. Tackling non-metastatic castration-resistant prostate cancer: special considerations in treatment. Expert Rev Anticancer Ther. 2017;17(7):625-633. https://doi.org/10.1080/14737140.2017.1333903 PMID:28532278 DOI: https://doi.org/10.1080/14737140.2017.1333903

Iacovelli R, Ciccarese C, Mosillo C, et al. Comparison Between Prognostic Classifications in De Novo Metastatic Hormone Sensitive Prostate Cancer. Target Oncol. 2018;13(5):649-655. https://doi.org/10.1007/s11523-018-0588-8 PMID:30167971 DOI: https://doi.org/10.1007/s11523-018-0588-8

Gravis G, Boher JM, Joly F, et al; GETUG. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. 2016;70(2):256-262. https://doi.org/10.1016/j.eururo.2015.11.005 PMID:26610858 DOI: https://doi.org/10.1016/j.eururo.2015.11.005

Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746. https://doi.org/10.1056/NEJMoa1503747 PMID:26244877 DOI: https://doi.org/10.1056/NEJMoa1503747

James ND, Sydes MR, Clarke NW, et al; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177. https://doi.org/10.1016/S0140-6736(15)01037-5PMID:26719232

Aly M, Leval A, Schain F, et al. Survival in patients diagnosed with castration-resistant prostate cancer: a population-based observational study in Sweden. Scand J Urol. 2020;54(2):115-121. https://doi.org/10.1080/21681805.2020.1739139 PMID:32266854 DOI: https://doi.org/10.1080/21681805.2020.1739139

Chen J, Ni Y, Sun G, et al. Comparison of Current Systemic Combination Therapies for Metastatic Hormone-Sensitive Prostate Cancer and Selection of Candidates for Optimal Treatment: A Systematic Review and Bayesian Network Meta-Analysis. Front Oncol. 2020;10:519388. https://doi.org/10.3389/fonc.2020.519388 PMID:33072564 DOI: https://doi.org/10.3389/fonc.2020.519388

Gazzetta Ufficiale della Repubblica Italiana: GU n.115 del 18-5-2022. Online https://www.aifa.gov.it/documents/20142/847786/Determina_ERLEADA_GUn.115_18-5-2022.pdf (Accessed October 2022)

Gazzetta Ufficiale della Repubblica Italiana: GU n.248 del 16-10-2021. Online https://www.gazzettaufficiale.it/eli/gu/2021/10/16/248/sg/pdf (Accessed October 2022)

Gazzetta Ufficiale della Repubblica Italiana: GU n.128 del 3-6-2022. Online https://www.gazzettaufficiale.it/eli/gu/2022/06/03/128/sg/pdf (Accessed October 2022)

Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986. https://doi.org/10.1200/JCO.19.00799 PMID:31329516 DOI: https://doi.org/10.1200/JCO.19.00799

Armstrong AJ, Azad AA, Iguchi T, et al. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022;40(15):1616-1622. https://doi.org/10.1200/JCO.22.00193 PMID:35420921 DOI: https://doi.org/10.1200/JCO.22.00193

Davis ID, Martin AJ, Stockler MR, et al; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121-131. https://doi.org/10.1056/NEJMoa1903835 PMID:31157964 DOI: https://doi.org/10.1056/NEJMoa1903835

Parker C, Castro E, Fizazi K, et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(9):1119-1134. https://doi.org/10.1016/j.annonc.2020.06.011 PMID:32593798 DOI: https://doi.org/10.1016/j.annonc.2020.06.011

Gazzetta Ufficiale della Repubblica Italiana GU n.272 del 31-10-2020. Online https://www.gazzettaufficiale.it/eli/gu/2020/10/31/272/sg/pdf (Accessed March 2023)

Riassunto delle caratteristiche del prodotto. Cabazitaxel. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_003792_041013_RCP.pdf&sys=m0b1l3 (Accessed October 2022)

Kerney, data on file. 2020.

Beca J, Majeed H, Chan KKW, Hotte SJ, Loblaw A, Hoch JS. Cost-effectiveness of docetaxel in high-volume hormone-sensitive metastatic prostate cancer. Can Urol Assoc J 2019;13(12):396-40. https://doi.org/10.5489/cuaj.5889 DOI: https://doi.org/10.5489/cuaj.5889

Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. https://doi.org/10.1200/jco.2017.75.3657 PMID: 29384722 DOI: https://doi.org/10.1200/JCO.2017.75.3657

AIFA. Linee guida per la compilazione del dossier a supporto della domanda di rimborsabilità e prezzo di un medicinale ai sensi del D.M. 2 agosto 2019. https://www.aifa.gov.it/documents/20142/1283800/Linee_guida_dossier_domanda_rimborsabilita.pdf (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Xtandi. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000771_042868_RCP.pdf&sys=m0b1l3 (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Docetaxel. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_003821_043484_RCP.pdf&retry=0&sys=m0b1l3 (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Abiraterone. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_001306_041427_RCP.pdf&sys=m0b1l3 (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Apalutamide. Online. https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_001306_047525_RCP.pdf&sys=m0b1l3 (Accessed October 2022)

de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. https://doi.org/10.1016/s0140-6736(10)61389-x PMID:20888992 DOI: https://doi.org/10.1016/S0140-6736(10)61389-X

Ryan CJ, Smith MR, de Bono JS, et al; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148. https://doi.org/10.1056/NEJMoa1209096 PMID:23228172 DOI: https://doi.org/10.1056/NEJMoa1209096

Tannock IF, de Wit R, Berry WR, et al; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512. https://doi.org/10.1056/NEJMoa040720 PMID:15470213 DOI: https://doi.org/10.1056/NEJMoa040720

Chi KN, Agarwal N, Bjartell A, et al; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019;381(1):13-24. https://doi.org/10.1056/NEJMoa1903307 PMID:31150574 DOI: https://doi.org/10.1056/NEJMoa1903307

Devlin N, Herdman M, Pavesi M, et al. Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial. Health Qual Life Outcomes. 2017;15(1):130. https://doi.org/10.1186/s12955-017-0704-y PMID:28645287 DOI: https://doi.org/10.1186/s12955-017-0704-y

Supplemento ordinario n. 8 alla Gazzetta Ufficiale, Serie generale 23, 2013 – Tariffe Ospedaliere. Online https://www.gazzettaufficiale.it/eli/gu/2013/01/28/23/so/8/sg/pdf (Accessed October 2022)

Hechmati G, Cure S, Gouépo A, et al. Cost of skeletal-related events in European patients with solid tumours and bone metastases: data from a prospective multinational observational study. J Med Econ. 2013;16(5):691-700. https://doi.org/10.3111/13696998.2013.779921PMID:23441975 DOI: https://doi.org/10.3111/13696998.2013.779921

Favaretto A, Grossi F, Morabito A, Ravasio R. Il costo degli eventi avversi associati ad Afatinib, Erlotinib e Gefitinib nel rtattamento del tumore del polmone non a piccole cellule con mutazione EGFR. Glob Reg Health Technol Assess. 2017;4(1):e187-e196. https://doi.org/10.33393/grhta.2017.394 . DOI: https://doi.org/10.5301/grhta.5000270

Vouk K, Benter U, Amonkar MM, et al. Cost and economic burden of adverse events associated with metastatic melanoma treatments in five countries. J Med Econ. 2016;19(9):900-912. https://doi.org/10.1080/13696998.2016.1184155 PMID:27123564 DOI: https://doi.org/10.1080/13696998.2016.1184155

Sferrazza A, Nicolotti N, Thiene DD, Veneziano MA, Capri S, de Waure C, et al. L’osteoporosi in Italia: risorse utilizzate dal SSN e relativi costi. Italian Journal of Public Health. 2011;8(Suppl.2):23-24.

Supplemento ordinario n. 8 alla Gazzetta Ufficiale, Serie generale 23, 2013 – Tariffe Ambulatoriali. https://www.gazzettaufficiale.it/eli/gu/2013/01/28/23/so/8/sg/pdf (Accessed October 2022)

Sathianathen NJ, Koschel S, Thangasamy IA, et al. Indirect Comparisons of Efficacy between Combination Approaches in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis. Eur Urol. 2020;77(3):365-372. https://doi.org/10.1016/j.eururo.2019.09.004 PMID:31679970 DOI: https://doi.org/10.1016/j.eururo.2019.09.004

Agenzia Italiana del Farmaco (AIFA). Elenco dei farmaci in classe A. Online: https://www.aifa.gov.it/liste-farmaci-a-h (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Ranitidina. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_002753_035702_RCP.pdf&retry=0&sys=m0b1l3 (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Ondansteron. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000040_040013_RCP.pdf&retry=0&sys=m0b1l3 (Accessed October 2022)

Riassunto delle caratteristiche del prodotto. Filgrastim. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_002317_027772_RCP.pdf&sys=m0b1l3 (Accessed October 2022)

IQVIA sales data. Data on file. 2021.

Chini F, Farchi S, Camilloni L, Giarrizzo ML, Giorgi Rossi P. Health care costs and functional outcomes of road traffic injuries in the Lazio region of Italy. Int J Inj Contr Saf Promot. 2016;23(2):145-154. https://doi.org/10.1080/17457300.2014.942324 PMID:25262669 DOI: https://doi.org/10.1080/17457300.2014.942324

MEF. Retribuzioni medie pro-capite medici 2016 Conto Annuale [Internet]. Online: https://contoannuale.rgs.mef.gov.it/ (Accessed October 2022)

ARAN. Contratto Collettivo nazionale di Lavoro del comparto SANITA’. Triennio 2016-2018 CCNL comparto Sanità. Online: https://www.aranagenzia.it/attachments/article/9016/CCNL%20comparto%20SANITA'%20definitivo_sito%20.pdf (Accessed October 2022)



How to Cite

Fiorentino F, Di Rienzo P. Budget impact analysis of enzalutamide for the treatment of hormone-sensitive metastatic prostate cancer in Italy. Grhta [Internet]. 2023 Apr. 11 [cited 2023 Jun. 8];10(1):29-3. Available from: https://journals.aboutscience.eu/index.php/grhta/article/view/2507

Most read articles by the same author(s)