Cost-utility analysis of brigatinib compared to alectinib in the treatment of ALK-positive NSCLC in patients previously not treated with an ALK inhibitor
DOI:
https://doi.org/10.33393/ao.2022.2450Keywords:
Alectinib, ALK-positive, Brigatinib, Cost-utility, Italian NHS, NSCLCAbstract
Objective: The aim of this economic evaluation was to assess the cost-utility of brigatinib versus alectinib in the treatment of naïve patients to anaplastic lymphoma kinase-positive advanced non-small cell lung cancer (ALK-positive aNSCLC) from the perspective of the Italian National Health Service (INHS).
Methods: A partitioned survival model with four health states (progression-free [PFS], no central nervous system progression [CNS-PFS], central nervous system progression [CNS-PD] and death) was used. The clinical data (progression-free survival, overall survival and time to progression) was based on the ALTA-1L trial for brigatinib and on ALEX trial for alectinib. Utility values were derived from EORTC QLQ-C30 scores evaluated in the ALTA-1L trial and literature. Costs included frontline therapies, subsequent therapies, best supportive care (BSC), administration, concomitant medications, adverse events and health states. Direct medical costs and benefits (quality-adjusted life-years, QALYs) were discounted at a 3.0% annual rate. Uncertainty was assessed using deterministic (DSA) and probabilistic sensitivity analyses (PSA).
Results: The analysis showed that brigatinib was dominant versus alectinib; brigatinib led to a gain of 0.216 QALYs and to a treatment cost reduction of € 85,635. The results of the DSA showed that no parameters of the model significantly modified the base case result.
Conclusions: This economic evaluation suggested that, compared with alectinib, brigatinib can be considered a valid cost-utility option from the perspective of INHS in the treatment of patients with ALK-positive aNSCLC.
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I numeri del cancro in Italia 2021. https://www.aiom.it/wp-content/uploads/2021/10/2021_NumeriCancro_web.pdf (Accessed June 2022)
Associazione Italiana di Oncologia Medica (AIOM) Linee guida neoplasie del polmone. Edizione 2021 aggiornata ad ottobre 2021. https://snlg.iss.it/wp-content/uploads/2021/11/LG-149_Polmone_agg2021.pdf (Accessed June 2022)
Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2016. https://seer.cancer.gov/csr/1975_2016/ (Accessed June 2022)
Barlesi F, Mazieres J, Merlio JP, et al; Biomarkers France contributors. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016;387(10026):1415-1426. https://doi.org/10.1016/S0140-6736(16)00004-0 PMID:26777916 DOI: https://doi.org/10.1016/S0140-6736(16)00004-0
Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14(13):4275-4283. https://doi.org/10.1158/1078-0432.CCR-08-0168 PMID:18594010 DOI: https://doi.org/10.1158/1078-0432.CCR-08-0168
Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013;19(15):4273-4281. https://doi.org/10.1158/1078-0432.CCR-13-0318PMID:23729361 DOI: https://doi.org/10.1158/1078-0432.CCR-13-0318
Reck M, Paz-Ares L. Immunologic checkpoint blockade in lung cancer. Semin Oncol. 2015;42(3):402-417. https://doi.org/10.1053/j.seminoncol.2015.02.013 PMID:25965358 DOI: https://doi.org/10.1053/j.seminoncol.2015.02.013
Gridelli C, de Marinis F, Cappuzzo F, et al. Treatment of advanced non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation or ALK gene rearrangement: results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2014;15(3):173-181. https://doi.org/10.1016/j.cllc.2013.12.002 PMID:24486058 DOI: https://doi.org/10.1016/j.cllc.2013.12.002
Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8(7):823-859. https://doi.org/10.1097/JTO.0b013e318290868f PMID:23552377 DOI: https://doi.org/10.1097/JTO.0b013e318290868f
Crizotinib (XALKORI®) Riassunto delle caratteristiche di prodotto. https://www.ema.europa.eu/en/documents/product-information/xalkori-epar-product-information_it.pdf (Accessed June 2022)
Solomon BJ, Mok T, Kim DW, et al; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. https://doi.org/10.1056/NEJMoa1408440 PMID:25470694 DOI: https://doi.org/10.1056/NEJMoa1408440
Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472-1482. https://doi.org/10.1158/1078-0432.CCR-11-2906 PMID:22235099 DOI: https://doi.org/10.1158/1078-0432.CCR-11-2906
Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(7):874-886. https://doi.org/10.1016/S1470-2045(17)30339-X PMID:28602779 DOI: https://doi.org/10.1016/S1470-2045(17)30339-X
Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018;29(6):1409-1416. https://doi.org/10.1093/annonc/mdy121PMID:29668860 DOI: https://doi.org/10.1093/annonc/mdy121
Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. J Clin Oncol. 2017;35(22):2490-2498. https://doi.org/10.1200/JCO.2016.71.5904PMID:28475456 DOI: https://doi.org/10.1200/JCO.2016.71.5904
Alectinib (ALECENSA®) Riassunto delle caratteristiche di prodotto. https://www.ema.europa.eu/en/documents/product-information/alecensa-epar-product-information_it.pdf (Accessed June 2022)
Brigatinib (ALUNBRIG®) Riassunto delle caratteristiche di prodotto. https://www.ema.europa.eu/en/documents/product-information/alunbrig-epar-product-information_it.pdf (Accessed June 2022)
Peters S, Camidge DR, Shaw AT, et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. 2017;377(9):829-838. https://doi.org/10.1056/NEJMoa1704795 PMID:28586279 DOI: https://doi.org/10.1056/NEJMoa1704795
Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non–small-cell lung cancer. N Engl J Med. 2018;379(21):2027-2039. https://doi.org/10.1056/NEJMoa1810171 PMID:30280657 DOI: https://doi.org/10.1056/NEJMoa1810171
Fattore G. Proposta di linee guida per la valutazione economica degli interventi sanitari in Italia. Pharmacoeconomics-Ital-Res-Articles. 2009;11:83-93. https://doi.org/10.1007/BF03320660 DOI: https://doi.org/10.1007/BF03320660
Takeda Pharmaceuticals Ltd. Clinical Study Report AP26113-13-301: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in Patients with ALK-positive Advanced Lung Cancer. 2020
Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced Non–Small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019;14(7):1233-1243. https://doi.org/10.1016/j.jtho.2019.03.007 PMID:30902613 DOI: https://doi.org/10.1016/j.jtho.2019.03.007
Mok TSK, Shaw AT, Camidge RD, et al. updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC. Ann Oncol. 2019;30(Supp.5):v607. https://doi.org/10.1093/annonc/mdz260.006 DOI: https://doi.org/10.1093/annonc/mdz260.006
Peters S, Mok TSK, Gadgeel SM, et al. Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC. J Clin Oncol. 2020;38(Suppl. 15):9518-9518. https://doi.org/10.1200/JCO.2020.38.15_suppl.9518 DOI: https://doi.org/10.1200/JCO.2020.38.15_suppl.9518
National Institute for Health and Care Excellence (NICE). Alectinib for untreated ALK-positive advanced non-small-cell lung cancer [TA536] published 08/08/2018. Online https://www.nice.org.uk/guidance/ta536 (Accessed June 2022)
Longworth L, Yang Y, Young T, et al. Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: a systematic review, statistical modelling and survey. Health Technol Assess. 2014;18(9):1-224. https://doi.org/10.3310/hta18090PMID:24524660 DOI: https://doi.org/10.3310/hta18090
Arnold DT, Rowen D, Versteegh MM, Morley A, Hooper CE, Maskell NA. Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in malignant mesothelioma. Health Qual Life Outcomes. 2015;13(1):6. https://doi.org/10.1186/s12955-014-0196-yPMID:25613110 DOI: https://doi.org/10.1186/s12955-014-0196-y
Ara RW. A., NICE DSU Technical Support Document 12: the use of health state utility values in decision models. School of Health and Related Research, University of Sheffield; 2011.
Roughley A, Damonte E, Taylor-Stokes G, Rider A, Munk VC. Impact of Brain Metastases on Quality of Life and Estimated Life Expectancy in Patients with Advanced Non-Small Cell Lung Cancer. Value Health. 2014;17(7):A650. https://doi.org/10.1016/j.jval.2014.08.2364PMID:27202347 DOI: https://doi.org/10.1016/j.jval.2014.08.2364
Blackhall F, Kim DW, Besse B, et al. Patient-reported outcomes and quality of life in PROFILE 1007: a randomized trial of crizotinib compared with chemotherapy in previously treated patients with ALK-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2014;9(11):1625-1633. https://doi.org/10.1097/JTO.0000000000000318 PMID:25436797 DOI: https://doi.org/10.1097/JTO.0000000000000318
Nafees B, Stafford M, Gavriel S, Bhalla S, Watkins J. Health state utilities for non small cell lung cancer. Health Qual Life Outcomes. 2008;6(1):84. https://doi.org/10.1186/1477-7525-6-84PMID:18939982 DOI: https://doi.org/10.1186/1477-7525-6-84
Ara R, Brazier JE. Using health state utility values from the general population to approximate baselines in decision analytic models when condition-specific data are not available. Value Health. 2011;14(4):539-545. https://doi.org/10.1016/j.jval.2010.10.029 PMID:21669378 DOI: https://doi.org/10.1016/j.jval.2010.10.029
Regime di rimborsabilità e prezzo, a seguito di nuove indicazioni terapeutiche, del medicinale per uso umano «Alunbrig». (Determina n. DG/1200/2020). (20A06597) (GU Serie Generale n.305 del 09-12-2020). Online https://www.gazzettaufficiale.it/eli/id/2020/12/09/20A06597/sg (Accessed June 2022)
Classificazione del medicinale per uso umano «Alecensa», ai sensi dell'articolo 8, comma 10, della legge 24 dicembre 1993, n. 537. (Determina n. 1124/2018). (18A05072) (GU Serie Generale n.176 del 31-07-2018). Online https://www.gazzettaufficiale.it/eli/id/2018/07/31/18A05072/sg (Accessed June 2022)
National Institute for Health and Care Excellence (NICE). Atezolizumab for treating locally advanced or metastatic non-small-cell lung cancer after chemotherapy [TA520] published 05/16/2018. Online https://www.nice.org.uk/guidance/ta520 (Accessed June 2022)
Reck M, Kaiser R, Mellemgaard A, et al; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15(2):143-155. https://doi.org/10.1016/S1470-2045(13)70586-2 PMID:24411639 DOI: https://doi.org/10.1016/S1470-2045(13)70586-2
National Institute for Health and Care Excellence (NICE). Nintedanib for previously treated locally advanced, metastatic, or locally recurrent non small cell lung cancer [TA347] published 07/22/2015. Online https://www.nice.org.uk/guidance/ta347 (Accessed June 2022)
Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917-929. https://doi.org/10.1016/S0140-6736(17)30123-X PMID:28126333 DOI: https://doi.org/10.1016/S0140-6736(17)30123-X
National Institute for Health and Care Excellence (NICE). Brigatinib for treating ALK-positive advanced non-small-cell lung cancer after crizotinib [TA571] published 03/20/2019. Online https://www.nice.org.uk/guidance/TA571 (Accessed June 2022)
Nomenclatore Tariffario – Regione Lombardia. Online https://www.regione.lombardia.it/wps/wcm/connect/4d9e0b94-a386-4f8d-9afd-a7b41a47738d/nomenclatore+tariffario+specialistica+ambulatoriale20210923.xlsx?MOD=AJPERES&CACHEID=ROOTWORKSPACE-4d9e0b94-a386-4f8d-9afd-a7b41a47738d-nMioG8r (Accessed June 2022)
Ravasio R, Tiseo M, Pradelli L et al. Cost-effectiveness analysis of alectinib versus crizotinib in first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer. Glob Reg Health Technol Assess. 2019;6:1-11. https://doi.org/10.33393/grhta.2019.462
Favaretto A, Grossi F, Morabito A, Ravasio R. Il costo degli eventi avversi associati ad afatinib, erlotinib e gefitinib nel trattamento del tumore del polmone non a piccole cellule con mutazione EGFR. Glob Reg Health Technol Assess. 2017;4(1):e187-e196. https://doi.org/10.5301/grhta.5000270 DOI: https://doi.org/10.5301/grhta.5000270
Remunerazione delle prestazioni di assistenza ospedaliera per acuti, assistenza ospedaliera di riabilitazione e di lungodegenza post acuzie e di assistenza specialistica ambulatoriale. Supplemento ordinario n.8 alla Gazzetta Ufficiale n. 23 del 28 gennaio 2013, Serie generale. Online https://www.gazzettaufficiale.it/eli/gu/2013/01/28/23/so/8/sg/pdf (Accessed June 2022
Associazione Italiana di Oncologia Medica (AIOM). Linee guida Neoplasie del Polmone. Edizione 2021, aggiornata a ottobre 2021. Online https://snlg.iss.it/wp-content/uploads/2021/11/LG-149_Polmone_agg2021.pdf (Accessed June 2022)
Lorlatinib (LORVIQUA®) Riassunto delle caratteristiche di prodotto. https://www.ema.europa.eu/en/documents/product-information/lorviqua-epar-product-information_it.pdf (Accessed June 2022)
Giuliani J. Brigatinib is a cost-effective treatment in first-line anaplastic lymphoma kinase mutation-positive (ALK + ) advanced non-small cell lung cancer (NSCLC) with brain metastases. J Oncol Pharm Pract. 2022 Apr;28(3):691-694. https://doi.org/10.1177/10781552211073468 PMID: 34994227 DOI: https://doi.org/10.1177/10781552211073468
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Copyright (c) 2022 Roberto Ravasio, Holly Cranmer, Izzie Kearns , Raffaella Viti, Simone Corinti
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Accepted 2022-09-27
Published 2022-10-24
