Abstract
Introduction
The NCT00339183 trial demonstrated that adding panitumumab to fluorouracil, leucovorin and irinotecan (FOLFIRI) as a second-line therapy of wild-type RAS metastatic colorectal cancer (mCRC) increases the median progression-free survival (PFS). Nevertheless, panitumumab is not yet approved in China, and the costs and outcomes of the therapy are still unclear. We estimated the cost-effectiveness of this intervention from the perspective of Chinese health care systems by constructing two pricing scenarios for panitumumab. Scenario 1: Pricing is based on the price of a similar product (cetuximab) in China. Scenario 2: We estimated the value-based price.
Methods
A partitioned survival model was created based on the results of the NCT00339183 trial, which evaluated panitumumab plus FOLFIRI versus FOLFIRI. The model simulated the disease progression. We calculated medical costs from the perspectives of the Chinese health care systems. The primary outcome measures were costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs).
Results
In scenario 1, compared with FOLFIRI alone, FOLFIRI with panitumumab arm had an ICER of ¥1,539,988/QALY. The most influential factors were the mean overall survival (OS), utility before progression and cost of panitumumab. The probability of panitumumab plus FOLFIRI being cost-effective in China was 0% when the willingness-to-pay (WTP) threshold was ¥193,932/QALY. In scenario 2, when the cost of panitumumab was assumed to be ¥4032.61 or ¥5218.96 per cycle, the ICERs approximated the WTP thresholds of ¥193,932/QALY or ¥420,633/QALY, respectively. In this value-based pricing scenario, panitumumab plus FOLFIRI is estimated to be cost-effective.
Conclusion
We construct two pricing scenarios in China. In scenario 1, panitumumab plus FOLFIRI as a second-line therapy of mCRC provided an incremental benefit, but simultaneously increased costs (at the current price) even further. In scenario 2, when the value-based price was adopted, panitumumab plus FOLFIRI was estimated to be cost-effective. Our study establishes a pricing framework for new anticancer drugs to reflect the economics of drugs.
Trial Registration Number
NCT00339183.
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References
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China. CA Cancer J Clin. 2016;66:115–32.
Van Cutsem E, Nordlinger B, Cervantes A, et al. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010;21(Suppl 5):v93–7.
Brenner H, Bouvier AM, Foschi R, et al. Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study. Int J Cancer. 2012;131:1649–58.
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Colon Cancer. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 13 Dec 2018.
Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.
Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25:1658–64.
Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.
Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21:5469–79.
Wan XM, Peng LB, Ma JA, et al. Economic evaluation of nivolumab as a second-line treatment for advanced renal cell carcinoma from US and Chinese perspectives. Cancer. 2017;123(14):2634–41.
Hoyle M, Rogers G, Moxham T, et al. Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or -intolerant chronic phase chronic myeloid leukemia. Value Health. 2011;14:1057–67.
China Guidelines for Pharmcoeconomic Evaluation research group. China Guidelines for Pharmcoeconomic Evaluation. 1st ed. Beijing: China Center for Health Economic Research; 2011. p. 23–4.
Hoyle MW, Henley W. Improved curve fits to summary survival data: application to economic evaluation of health technologies. BMC Med Res Methodol. 2011;11:139.
Wan X, Peng L, Li Y. A review and comparison of methods for recreating individual patient data from published Kaplan–Meier survival curves for economic evaluations: a simulation study. PLoS One. 2015;10:e0121353.
Freeman K, Connock M, Cummins E, et al. Fluorouracil plasma monitoring: the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technol Assess. 2015;19:1–321 (v–vi).
Tikhonova IA, Huxley N, Snowsill T, et al. Economic analysis of first-line treatment with cetuximab or panitumumab for RAS wild-type metastatic colorectal cancer in England. Pharmacoeconomics. 2018;36:837–51.
Wu B, Dong B, Xu Y, et al. Economic evaluation of first-line treatments for metastatic renal cell carcinoma: a cost-effectiveness analysis in a healthresource-limited setting. PLoS One. 2012;7:e32530.
Li-xia L, Shu-hone B, Lan J, et al. Analysis on ADR treatment cost of the four chemotherapy regimens for colorectal cancer [Article in Chinese]. Zhongguo Yiyuan Yaoxue Zazhi. 2013;33:1795–8.
Xiao-hui W, Jun Z, Dong Z. Pharmacoeconomic research on adverse drug reactions of chemotherapy for lung cancer [Article in Chinese]. J Shanghai Jiaotong Univ. 2012;32:657–60.
Yu-ming J, Jun P, Ziping L, et al. Pharmacoeconomic research on adverse drug reactions of chemotherapy for lung cancer [Article in Chinese]. China Pharm. 2001;12:91–2.
Bennett L, Zhao Z, Barber B, et al. Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment. Br J Cancer. 2011;105:1495–502.
Wang J, Zhao Z, Barber B, et al. A Q-twist analysis comparing panitumumab plus best supportive care (BSC) with BSC alone in patients with wild-type KRAS metastatic colorectal cancer. Br J Cancer. 2011;104:1848–53.
National Bureau of Statistics of China. Health care and personal articles of consumer price indices. http://data.stats.gov.cn/search.htm?s=CPI. Accessed 20 July 2019.
Goldstein DA, Chen Q, Ayer T, et al. First- and second-line bevacizumab in addition to chemotherapy for metastatic colorectal cancer: a United States-based cost-effectiveness analysis. J Clin Oncol. 2015;33:1112–8.
Briggs A, Claxton C, Sculpher M. Decision Modeling for Health Economic Evaluation. Oxford, England: Oxford University Press; 2006.
Ocana A, Amir E, Tannock IF. Toward value-based pricing to boost cancer research and innovation. Cancer Res. 2016;76:3127–9.
National Institute for Health and Care Excellence. Cetuximab (review of TA176) and panitumumab (partial review of TA240) for the first line treatment of metastatic colorectal cancer [ID794]. https://www.nice.org.theUK/guidance/ta439/evidence. Accessed 14 May 2018.
World Health Organization. Choosing Interventions that are Cost Effective (WHO-CHOICE), Tables of costs and prices used in WHO-CHOICE analysis. https://www.who.int/entity/choice/costs/en/. Accessed 04 Sep 2019.
Eichler HG, Kong SX, Gerth WC, et al. Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health. 2004;7:518–28.
Murray CJ, Evans DB, Acharya A, et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9:235–51 (8.38).
Messori A, De Rosa M, Pani L. Alternative pricing strategies for cancer drugs. JAMA. 2015;313:857.
The Economist Intelligence Unit. Valuebased healthcare in France: a slow adoption of cost-effectiveness criteria. http://www.economistinsights.com/sites/default/files/ValuebasedhealthcareFrance.pdf. Accessed 9 Dec 2019.
Gerber A, Stock S, Dintsios CM. Reflections on the changing face of German pharmaceutical policy: How far is Germany from value-based pricing? Pharmacoeconomics. 2011;29:549–53.
Goldstein DA, Sarfaty M. Cancer drug pricing and reimbursement: lessons for the United States from around the world. Oncologist. 2016;21(8):907–9.
Dos Santos RF, Coutinho MB, Haas L. Panitumumab + Mfolfox6 versus bevacizumab + Mfolfox6 as first-line treatment of wild-type Ras metastatic colorectal cancer: a cost-effectiveness analysis from the Brazilian Private Healthcare System Perspective. Value Health. 2015;18:A821.
Graham CN, Hechmati G, Hjelmgren J, et al. Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer. 2014;50:2791–801.
Fínek J, Skoupá J, Jandová P. Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared to bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer-Czech Republic model adaptation. Klin Onkol. 2015;28:265–72.
Ewara EM, Zaric GS, Welch S, et al. Cost-effectiveness of first-line treatments for patients with KRAS wild-type metastatic colorectal cancer. Curr Oncol. 2014;21:e541–50.
Suarez J. Cost-effectiveness analysis of cetuximab and panitumumab for first line treatment of metastatic colorectal cancer (Mcrc) in Wt Ras patients in Spain. Value Health. 2015;18:A460.
Vargas-Valencia J, Garcia Perlaza J. Cost-effectiveness analysis of Panitumumab + Folfox compared to Cetuximab + Folfiri as first-line treatment for patients with wild-type (Wt) Ras (Exons 2, 3, And 4 Of Kras And Nras) metastatic colorectal cancer (Mcrc) in Colombia. Value Health. 2015;18:A460.
Hoyle M, Peters J, Crathorne L, et al. Cost-effectiveness of cetuximab, cetuximab plus irinotecan, and panitumumab for third and further lines of treatment for KRAS wild-type patients with metastatic colorectal cancer. Value Health. 2013;16:288–96.
Drummond M, Barbieri M, Cook J, et al. Transferability of economic evaluations across jurisdictions: ISPOR Good Research Practices Task Force report. Value Health. 2009;12:409–18.
National Development and Reform Commission. Abolishment of government (guided) pricing for the majority of drugs and push to the drug pricing reform [in Chinese]. http://www.sdpc.gov.cn/xwzx/xwfb/201505/t20150505_690687.html. Accessed 13 Dec 2018.
State Council of the People’s Republic of China. China to cut prices of expensive patent drugs [in Chinese]. http://english.gov.cn/news/top_news/2016/05/20/content_281475353689066.html. Accessed 13 Dec 2018.
State Council of the People’s Republic of China. Notice of the State Council on issuing the 13th five-year plan on deepening the medical and health care system reform [in Chinese]. http://www.gov.cn/zhengce/content/2017-01/09/content_5158053.html. Accessed 13 Dec 2018.
Hawkins N, Scott DA. Reimbursement and value-based pricing: stratified cost-effectiveness analysis may not be the last word. Health Econ. 2011;20:688–98.
Ministry of Finance of the People’s Republic of China. Notice of the policy of added-value tax on anti-cancer drugs [in Chinese]. http://szs.mof.gov.cn/zhengwuxinxi/zhengcefabu/201804/t20180427_2880407.html. Accessed 13 Dec 2018.
Lee SG, Jee YG, Chung HC, et al. Cost-effectiveness analysis of adjuvant therapy for node positive breast cancer in Korea: docetaxel, doxorubicin and cyclophosphamide (TAC) versus fluororacil, doxorubicin and cyclophosphamide (FAC). Breast Cancer Res Treat. 2009;114:589–95.
Liubao P, Xiaomin W, Chongqing T, et al. Cost-effectiveness analysis of adjuvant therapy for operable breast cancer from a Chinese perspective: Doxorubicin plus Cyclophosphamide versus Docetaxel plus Cyclophosphamide. Pharmacoeconomics. 2009;27:873–86.
Goldstein DA, Chen Q, Ayer T, et al. Necitumumab in metastatic squamous cell lung cancer: establishing a value-based cost. JAMA Oncol. 2015;1:1293–300.
Acknowledgements
Funding
This work was supported by the National Natural Science Foundation of China (grant no. 81603081) and the Key Science-Technology Research and Development Program of Hunan Province (2016JC2062). The Rapid Service Fee was funded by the authors. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.
Disclosures
Yin Shi, Xiaomin Wan, Chongqing Tan, Jianhe Li and Liubao Peng have nothing to disclose.
Compliance with Ethics Guidelines
Because this model-based article does not contain any new studies with human or animal subjects performed by any of the authors, it does not require the approval of the independent ethics committee.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Shi, Y., Wan, X., Tan, C. et al. Model-Based Cost-Effectiveness Analysis of Panitumumab Plus FOLFIRI for the Second-Line Treatment of Patients with Wild-Type Ras Metastatic Colorectal Cancer. Adv Ther 37, 847–859 (2020). https://doi.org/10.1007/s12325-019-01214-y
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DOI: https://doi.org/10.1007/s12325-019-01214-y