Document Type : Original Article(s)

Authors

1 Department of Pharmacoeconomics and Pharmaceutical Management, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Pharmaceutical Management and Economic Research Center, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran

10.30476/mejc.2024.100077.1969

Abstract

Background: Metastatic colorectal cancer (mCRC) constitutes a significant health burden globally, accompanied by elevated mortality rates. This study aimed to assess the cost-effectiveness of Regorafenib, an orally administered multi-kinase inhibitor, compared to the combination of Cetuximab and Irinotecan (CetIri) as third-line therapy for mCRC in Iran.
Method: A model-based cost-utility analysis was conducted employing a semi-Markov model for a hypothetical cohort of 1,000 patients, integrating time-dependent transition probabilities. From the perspective of the Iranian healthcare payer, the analysis included direct medical costs, such as therapy, monitoring, and adverse effect-related expenses, sourced from national databases in Iran. A yearly discount rate of 5% was applied to both costs and outcomes. Data analysis utilized Microsoft Excel, R version 4.1.3, and TreeAge Pro Healthcare version 2022 software, with the significance threshold set at 0.05.
Results: The base-case analysis revealed that Regorafenib offers a cost saving of $12,154 and an incremental gain of 0.1 Quality-adjusted life years (QALYs) per patient over a 19-month horizon compared with the CetIri regimen. Probabilistic sensitivity analysis showed a greater than 99% probability of Regorafenib being cost-effective.
Conclusion: Consistent with existing evidence, the findings advocate Regorafenib as a cost-effective alternative to CetIri for third-line treatment of mCRC in Iran, considering the specific healthcare system context. Given the foundational assumptions, caution is advised when extrapolating these results to other regions.

Highlights

Meysam Seyedifar (PubMed)

Behzad Fatemi (PubMed)

Keywords

Main Subjects

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.100077.1969

Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Luo Q, O’Connell DL, Kahn C, Yu XQ. Colorectal cancer metastatic disease progression in Australia: A population-based analysis. Cancer Epidemiol. 2017;49:92-100. doi: 10.1016/j.canep.2017.05.012. Messersmith WA. NCCN guidelines updates: management of metastatic colorectal cancer. J Natl Compr Cancer Netw. 2019;17(5.5):599-601. doi: 10.6004/jnccn.2019.5014. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-422. doi: 10.1093/annonc/mdw235. Rey JB, Launay-Vacher V, Tournigand C. Regorafenib as a single-agent in the treatment of patients with gastrointestinal tumors: an overview for pharmacists. J Pharm Clin. 2014;33(4):189-205. doi: 10.1007/s11523-014-0333-x. Ettrich TJ, Seufferlein T. Regorafenib. Recent Results Cancer Res. 2018;211:45-56. doi: 10.1007/978-3-319-91442-8_3. Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619-29. doi: 10.1016/S1470-2045(15)70156-7. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Calcagno F, Lenoble S, Lakkis Z, Nguyen T, Limat S, Borg C, et al. Efficacy, safety and cost of Regorafenib in patients with metastatic colorectal cancer in French clinical practice. Clin Med Insights Oncol. 2016;10:59-66. doi: 10.4137/CMO.S38335. Sassi F. Calculating QALYs, comparing QALY and DALY calculations. Health Policy Plan. 2006;21(5):402-8. doi: 10.1093/heapol/czl018 Ministry of Health, Treatment, and Medical Education of Iran. [Internet] Tehran: 2021 Medical Services fact book; c2021 [cited 2021 Apr 28]. Available from: https://rvu.behdasht.gov.ir/ Iran Food and Drug Administration. [Internet] Tehran: Iran 2021 Pharmaceutical Statistics Fact Book; c2018 [cited 2022 Oct 28]. Available from: https://www.fda.gov.ir/fa/لینک-های-اداره-دارو/امار-و-اطلاعات-اداره-برنامه-ریزی The World bank Group. [Internet] Washington: PPP conversion factor, GDP (LCU per international $) - Iran, Islamic Rep; c2023 [cited 2022 Sep 26]. Available from: https://data.worldbank.org/indicator/PA.NUS.PPP?locations=IR Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, et al. Rectal cancer, version 2.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2018;16(7):874-901. doi: 10.6004/jnccn.2018.0061 Yoshino T, Arnold D, Taniguchi H, Pentheroudakis G, Yamazaki K, Xu RH, et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann Oncol. 2018;29(1):44-70. doi: 10.1093/annonc/mdx738. The World bank Group. [Internet] Washington: GDP per capita, PPP (current international $) - Iran, Islamic Rep; c2023 [cited 2022 Sep 26]. Available from: https://data.worldbank.org/indicator/NY.GDP.PCAP.PP.CD?locations=IR Vincenzi B, Santini D, Rabitti C, Coppola R, Beomonte Zobel B, Trodella L, et al. Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. Br J Cancer. 2006;94(6):792-7. doi: 10.1038/sj.bjc.6603018. Hoyle MW, Henley W. Improved curve fits to summary survival data: Application to economic evaluation of health technologies. BMC Med Res Methodol. 2011;11(1):139. doi: 10.1186/1471-2288-11-139. Liu J, Zhu S, Sun W, Tao L, Xiao D, Xuan J. Cost-effectiveness analysis of Regorafenib for third-line metastatic colorectal cancer (MCRC) compared to Cetuximab plus Irinotecan in China. Value Heal. 2018;21:S33. doi: 10.1016/j.jval.2018.04.215. Dhillon S. Regorafenib: a review in metastatic colorectal cancer. Drugs. 2018;78:1133-44. doi: 10.1007/s40265-018-0938-y. Neugut AI, Lin A, Raab GT, Hillyer GC, Keller D, O’Neil DS, et al. FOLFOX and FOLFIRI use in stage IV colon cancer: analysis of SEER-medicare data. Clin Colorectal Cancer. 2019;18(2):133–40. doi: 10.1016/j.clcc.2019.01.005 Velasco EM, Arnaiz IG, Teijeira L, Vera R. Regorafenib as third-line treatment for refractory metastatic colorectal cancer (mCRC): Experience of Hospital de Navarra clinical practice. Ann Oncol. 2017;28:iii109. doi: 10.1093/annonc/mdx261.308. Goldstein DA, Ahmad BB, Chen Q, Ayer T, Howard DH, Lipscomb J, et al. Cost-effectiveness analysis of Regorafenib for metastatic colorectal cancer. J Clin Oncol. 2015;33(32):3727-32. doi: 10.1200/JCO.2015.61.9569. Guan X, Li H, Xiong X, Peng C, Wang N, Ma X, et al. Cost-effectiveness analysis of fruquintinib versus regorafenib as the third-line therapy for metastatic colorectal cancer in China. J Med Econ. 2021;24(1):339-44. doi: 10.1080/13696998.2021.1888743.