Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage IV Hodgkin lymphoma in Italy
DOI:
https://doi.org/10.33393/grhta.2024.3167Keywords:
Brentuximab Vedotin, Cost-Effectiveness Analysis , Economic evaluation, Hodgkin lymphomaAbstract
Objectives: Advanced Hodgkin’s lymphoma (HL) is a rare severe neoplasm, significantly limiting the ability of patients to do daily activities among other impacts of the cancer. Many adult patients present with advanced stage disease (stages III/IV). This analysis investigates the cost-effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbarzine (AVD) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for the frontline treatment of stage IV HL in Italy based on data from the ECHELON-1 clinical trial.
Methods: The analysis was conducted from the perspective of the National Health Service using a Markov model with three mutually exclusive health states and a lifetime time horizon. Transition probabilities were taken from the six-year follow-up data of ECHELON-1. Costs were obtained mainly from published literature and national tariffs. For all drugs, ex-factory prices net of the mandatory reductions required by law were considered. Scenarios on possible confidential drug discounts were also explored.
Results: BV in combination with AVD was associated with an increase of € 44,551 in total costs of 1.03 life-years (LYs) and 0.85 quality-adjusted life-years (QALYs) as compared with ABVD in the base-case scenario. The incremental cost-effectiveness ratio and the incremental cost-utility ratio were estimated equal to € 43,179/LYs and € 52,257/QALYs, respectively, when based on ex-factory prices. BV in combination with AVD was shown to be a cost-effective option in 24 out of 36 scenarios examining possible confidential discounts (ranging from 0% to 60%) for high-cost drugs included in the analysis based on a € 41,411/QALYs threshold for severe diseases.
Conclusions: Based on data from 6 years of follow-up from the ECHELON-1 trial, BV in combination with AVD has the potential to be a cost-effective option versus ABVD for the frontline treatment of stage IV HL in Italy.
Downloads
References
Smith A, Crouch S, Lax S, et al. Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the UK’s Haematological Malignancy Research Network. Br J Cancer. 2015;112(9):1575-1584. https://doi.org/10.1038/bjc.2015.94 PMID:25867256 DOI: https://doi.org/10.1038/bjc.2015.94
Hanly P, Soerjomataram I, Sharp L. Measuring the societal burden of cancer: the cost of lost productivity due to premature cancer-related mortality in Europe. Int J Cancer. 2015;136(4):E136-E145. https://doi.org/10.1002/ijc.29105 PMID:25066804 DOI: https://doi.org/10.1002/ijc.29105
HMRN. R. HMRN incidence - Classical Hodgkin lymphoma. 2022; Online https://hmrn.org/statistics/incidence. (Accessed June 2024)
AIOM. I numeri del cancro in Italia 2023. Online https://www.aiom.it/i-numeri-del-cancro-in-italia/. (Accessed June 2024)
International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987-994. https://doi.org/10.1056/NEJM199309303291402 PMID:8141877 DOI: https://doi.org/10.1056/NEJM199309303291402
Koshy M, Fairchild A, Son CH, Mahmood U. Improved survival time trends in Hodgkin’s lymphoma. Cancer Med. 2016;5(6):997-1003. https://doi.org/10.1002/cam4.655 PMID:26999817 DOI: https://doi.org/10.1002/cam4.655
Behringer K, Mueller H, Goergen H, et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol. 2013;31(2):231-239. https://doi.org/10.1200/JCO.2012.44.3721 PMID:23150709 DOI: https://doi.org/10.1200/JCO.2012.44.3721
Ansell SM, Radford J, Connors JM, et al; ECHELON-1 Study Group. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2022;387(4):310-320. https://doi.org/10.1056/NEJMoa2206125 PMID:35830649 DOI: https://doi.org/10.1056/NEJMoa2206125
European Medicines Agency. EPAR, ADCETRIS. Online https://www.ema.europa.eu/en/documents/variation-report/adcetris-h-c-002455-ii-0055-epar-assessment-report-variation_en.pdf. (Accessed June 2024)
ISTAT. Tavola di mortalità. Anno 2022. Online http://dati.istat.it/Index.aspx?DataSetCode=DCIS_MORTALITA1. (Accessed June 2024)
Latimer NR. Survival analysis for economic evaluations alongside clinical trials--extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med Decis Making. 2013;33(6):743-754. https://doi.org/10.1177/0272989X12472398 PMID:23341049 DOI: https://doi.org/10.1177/0272989X12472398
Capri S, Ceci A, Terranova L, Merlo F, Mantovani L. Guidelines for economic evalu-ations in Italy: recommendations from the Italian Group of phar-macoeconomic studies. Drug Inf J. 2001;35(1):189-201. https://doi.org/10.1177/009286150103500122 DOI: https://doi.org/10.1177/009286150103500122
Associazione Italiana di Economia Sanitaria (AIES). Proposta di lineeguida per la valutazione economica degli interventi sanitari. Politiche Sanitarie. 2009;10:91-99.
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. Online https://www.aifa.gov.it/documents/20142/1283800/Linee_guida_dossier_domanda_rimborsabilita.pdf. (Accessed June 2024)
Blank O, von Tresckow B, Monsef I, Specht L, Engert A, Skoetz N. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2017;4(4):CD007110. https://doi.org/10.1002/14651858.CD007110.pub3 PMID:28447341 DOI: https://doi.org/10.1002/14651858.CD007110.pub3
Allen PB, Gordon LI. Frontline Therapy for Classical Hodgkin Lymphoma by Stage and Prognostic Factors. Clin Med Insights Oncol. 2017;11:1179554917731072. https://doi.org/10.1177/1179554917731072 PMID:28989291 DOI: https://doi.org/10.1177/1179554917731072
Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562-1566. https://doi.org/10.1182/blood-2016-02-699850 PMID:27432875 DOI: https://doi.org/10.1182/blood-2016-02-699850
Straus DJ, Długosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8(6):e410-e421. https://doi.org/10.1016/S2352-3026(21)00102-2 PMID:34048680 DOI: https://doi.org/10.1016/S2352-3026(21)00102-2
Dores GM, Curtis RE, Dalal NH, Linet MS, Morton LM. Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016. J Clin Oncol. 2020;38(35):4149-4162. https://doi.org/10.1200/JCO.20.00264 PMID:32946352 DOI: https://doi.org/10.1200/JCO.20.00264
Scalone L, Cortesi PA, Ciampichini R, Cesana G, Mantovani LG. Health Related Quality of Life norm data of the Italian general population: results using the EQ-5D-3L and EQ-5D-5L instruments. Epidemiol Biostat Public Health. 2022;12(3). https://doi.org/10.2427/11457 DOI: https://doi.org/10.2427/11457
Connors JM, Jurczak W, Straus DJ, et al; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2018;378(4):331-344. https://doi.org/10.1056/NEJMoa1708984 PMID:29224502 DOI: https://doi.org/10.1056/NEJMoa1708984
Decreto del Ministero della Salute 18 ottobre 2012. Tariffe delle prestazioni di assistenza specialistica ambulatoriale. Online http://www.trovanorme.salute.gov.it/norme/renderPdf.spring?seriegu=SG&datagu=28/01/2013&redaz=13A00528&artp=3&art=1&subart=1&subart1=10&vers=1&prog=001 (Accessed June 2024)
Eichenauer DA, Aleman BMP, André M, et al; ESMO Guidelines Committee. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(suppl 4):iv19-iv29. https://doi.org/10.1093/annonc/mdy080 PMID:29796651 DOI: https://doi.org/10.1093/annonc/mdy080
Berger MJ, Ettinger DS, Aston J, et al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017;15(7):883-893. https://doi.org/10.6004/jnccn.2017.0117 PMID:28687576 DOI: https://doi.org/10.6004/jnccn.2017.0117
AIOM. Linee guida terapia antiemetica. Edizione; 2018. Online https://www.aiom.it/wp-content/uploads/2018/11/2018_LG_AIOM_Antiemetica.pdf (Accessed June 2024)
AIFA. RCP ACICLOVIR. Online https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_001561_032307_RCP.pdf&sys=m0b1l3. (Accessed June 2024)
Petrosillo N. Therapy and prophylaxis of bacterial infections of the onco-haematological patient. Trends Med. 2011;11(4):179-184. Online https://www.oatext.com/pdf/TiM-11-418.pdf (Accessed June 2024)
AIOM. Linee guida gestione della tossicità ematopoietica in oncologia. Edizione 2018. Online https://www.aiom.it/wp-content/uploads/2019/01/2018_LG_AIOM_TossEmatopoietica.pdf. (Accessed June 2024)
AIOM. Terapia del dolore in oncologia. Edizione 2019. Online https://www.aiom.it/wp-content/uploads/2019/10/2019_LG_AIOM_Terapia_dolore.pdf. (Accessed June 2024)
Decreto del Ministero della Salute 18 ottobre 2012. Tariffe delle prestazioni di assistenza ospedaliera per acuti, per tipo di ricovero. Online http://www.trovanorme.salute.gov.it/norme/renderPdf.spring?seriegu=SG&datagu=28/01/2013&redaz=13A00528&artp=1&art=1&subart=1&subart1=10&vers=1&prog=001. (Accessed June 2024)
Ministero della Salute. Rapporto annuale sull’attività di ricovero ospedaliero. DATI SDO 2020. Online https://www.salute.gov.it/imgs/C_17_pubblicazioni_3277_allegato.pdf. (Accessed June 2024)
Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190. https://doi.org/10.1200/JCO.2010.28.1618 PMID:20660832 DOI: https://doi.org/10.1200/JCO.2010.28.1618
Armand P, Engert A, Younes A, et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018;36(14):1428-1439. https://doi.org/10.1200/JCO.2017.76.0793 PMID:29584546 DOI: https://doi.org/10.1200/JCO.2017.76.0793
Kuruvilla J, Ramchandren R, Santoro A, et al; KEYNOTE-204 investigators. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22(4):512-524. https://doi.org/10.1016/S1470-2045(21)00005-X PMID:33721562 DOI: https://doi.org/10.1016/S1470-2045(21)00005-X
Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183-2189. https://doi.org/10.1200/JCO.2011.38.0410 PMID:22454421 DOI: https://doi.org/10.1200/JCO.2011.38.0410
Moskowitz AJ, Hamlin PA Jr, Perales MA, et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2013;31(4):456-460. https://doi.org/10.1200/JCO.2012.45.3308 PMID:23248254 DOI: https://doi.org/10.1200/JCO.2012.45.3308
Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica. 2007;92(1):35-41. https://doi.org/10.3324/haematol.10661 PMID:17229633 DOI: https://doi.org/10.3324/haematol.10661
Crump M, Kuruvilla J, Couban S, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490-3496. https://doi.org/10.1200/JCO.2013.53.9593 PMID:25267740 DOI: https://doi.org/10.1200/JCO.2013.53.9593
Russo P, Zanuzzi M, Carletto A, Sammarco A, Romano F, Manca A. Role of Economic Evaluations on Pricing of Medicines Reimbursed by the Italian National Health Service. PharmacoEconomics. 2023;41(1):107-117. https://doi.org/10.1007/s40273-022-01215-w PMID:36434415 DOI: https://doi.org/10.1007/s40273-022-01215-w
Lazzaro C, Barone C, Caprioni F, et al. An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) + gemcitabine vs gemcitabine alone for metastatic pancreatic cancer patients: the APICE study. Expert Rev Pharmacoecon Outcomes Res. 2018;18(4):435-446. https://doi.org/10.1080/14737167.2018.1464394 PMID:29641931 DOI: https://doi.org/10.1080/14737167.2018.1464394
Pradelli L, Bellone M, Sanchez Alvarez J, Leibfried M, Caputo A. POSB108 Cost-Effectiveness and Cost-Utility Analyses of Atezolizumab-Based Therapy in Patients with Advanced or Unresectable Hepatocellular Carcinoma in Italy. Value Health. 2022;25(1):S82. https://doi.org/10.1016/j.jval.2021.11.381 DOI: https://doi.org/10.1016/j.jval.2021.11.381
Russo P. How reliable are ICER’s results published in current pharmacoeconomic literature? The controversial issue of price confidentiality. Glob Reg Health Technol Assess. 2022;9:31-35. https://doi.org/10.33393/grhta.2022.2350 PMID:36628320 DOI: https://doi.org/10.33393/grhta.2022.2350
Huntington SF, von Keudell G, Davidoff AJ, Gross CP, Prasad SA. Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma. J Clin Oncol. 2018;36(33):JCO1800122. https://doi.org/10.1200/JCO.18.00122 PMID:30285558 DOI: https://doi.org/10.1200/JCO.18.00122
Raymakers AJN, Costa S, Cameron D, Regier DA. Cost-effectiveness of brentuximab vedotin in advanced stage Hodgkin’s lymphoma: a probabilistic analysis. BMC Cancer. 2020;20(1):992. https://doi.org/10.1186/s12885-020-07374-3 PMID:33050897 DOI: https://doi.org/10.1186/s12885-020-07374-3
Delea TE, Sharma A, Grossman A, et al. Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma. J Med Econ. 2019;22(2):117-130. https://doi.org/10.1080/13696998.2018.1542599 PMID:30375910 DOI: https://doi.org/10.1080/13696998.2018.1542599
Vijenthira A, Chan K, Cheung MC, Prica A. Cost-effectiveness of first-line treatment options for patients with advanced-stage Hodgkin lymphoma: a modelling study. Lancet Haematol. 2020;7(2):e146-e156. https://doi.org/10.1016/S2352-3026(19)30218-2 PMID:31948928 DOI: https://doi.org/10.1016/S2352-3026(19)30218-2
National Cancer Institute. Hodgkin Lymphoma, SEER Survival Rates by Time Since Diagnosis, 2000-2018, By Stage at Diagnosis. 2018; Online https://seer.cancer.gov/explorer/application.php. (Accessed June 2024)
Pan-Canadian Oncology Drug Review. pCODR Expert Review Committee (pERC). Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the treatment of previously untreated patients with stage IV Hodgkin lymphoma (HL). Final Recommendation. Online https://www.cadth.ca/sites/default/files/pcodr/Reviews2020/10214BrentuximabVedotinHLAVD_FnRec_approvedbyChair_REDACT_Post03Dec2020_final.pdf. (Accessed June 2024)
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2024 The authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Accepted 2024-10-31
Published 2024-12-10
