Cost-effectiveness and safety of the molecular targeted drugs afatinib, gefitinib and erlotinib as first-line treatments for patients with advanced EGFR mutation-positive non-small-cell lung cancer

Kimura,M.; Yasue,F.; Usami,E.; Kawachi,S.; Iwai,M.; Go,M.; Ikeda,Y.; Yoshimura,T.

doi:10.3892/mco.2018.1640

Cost-effectiveness and safety of the molecular targeted drugs afatinib, gefitinib and erlotinib as first-line treatments for patients with advanced EGFR mutation-positive non-small-cell lung cancer

Authors:
- M. Kimura
- F. Yasue
- E. Usami
- S. Kawachi
- M. Iwai
- M. Go
- Y. Ikeda
- T. Yoshimura
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Affiliations: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki-shi, Gifu 503-8502, Japan, Faculty of Pharmaceutical Sciences, Kinjo Gakuin University, Nagoya-shi, Aichi 463-8521, Japan
Published online on: May 30, 2018 https://doi.org/10.3892/mco.2018.1640
Pages: 201-206

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Abstract

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, erlotinib and afatinib are standard first-line treatments for EGFR gene mutation-positive non-small cell lung cancer. The present study aimed to compare the cost-effectiveness of using erlotinib, afatinib or gefitinib. The safety of EGFR-TKIs was also investigated. Expected costs were calculated based on data from patients with advanced EGFR mutation-positive non‑small‑cell lung cancer who were treated with gefitinib, erlotinib or afatinib. Literature was collected to obtain the necessary clinical information for calculating the probability and the validity of each chemotherapy. Median survival time (MST) was used to evaluate the therapeutic effect of the regimens. The cost-effectiveness ratio was calculated using expected costs and MSTs for the three regimens. The cost-effectiveness ratio per month was JPY 386,859.4/MST for afatinib, JPY 264,788.7/MST for gefitinib and JPY 397,039.9/MST for erlotinib. Significant differences were observed between the three groups (p<0.001). The incremental cost-effectiveness ratio (ICER) of gefitinib compared with afatinib per month was JPY 122,070.7/MST. The ICER of gefitinib compared with erlotinib was JPY -69,605.9/MST. Adverse effects of Grade 3 and higher, including diarrhoea (28.6%) and paronychia (14.3%) were observed in the afatinib treatment group. Paronychia (23.1%) was observed in the erlotinib treatment group, while none were observed in the gefitinib treatment group. These findings demonstrate that gefitinib is more cost effective in comparison with the afatinib and erlotinib regimens, although the afatinib and erlotinib regimens were well-tolerated and produce sufficient effects.

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1	Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y and Fukuoka M: Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 18:317–323. 2007. View Article : Google Scholar : PubMed/NCBI
2	Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: North-East Japan Study Group: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI
3	Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, et al West Japan Oncology Group: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar : PubMed/NCBI
4	Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al: Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica: Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13:239–246. 2012. View Article : Google Scholar : PubMed/NCBI
5	Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, et al: First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: Analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 26:1883–1889. 2015. View Article : Google Scholar : PubMed/NCBI
6	Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, et al: Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 16:141–151. 2015. View Article : Google Scholar : PubMed/NCBI
7	Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M, Yang JC, Mok T, Lee KH, Lu S, et al: Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: Overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 28:270–277. 2017. View Article : Google Scholar : PubMed/NCBI
8	Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y and Yamamoto N: Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 106:1202–1211. 2015. View Article : Google Scholar : PubMed/NCBI
9	Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, et al: Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: Quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 17:863–870. 2012. View Article : Google Scholar : PubMed/NCBI
10	Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: North-East Japan Study Group: Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 24:54–59. 2013. View Article : Google Scholar : PubMed/NCBI
11	Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, et al: PROFILE 1014 Investigators: First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 371:2167–2177. 2014. View Article : Google Scholar : PubMed/NCBI
12	Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al: Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 373:123–135. 2015. View Article : Google Scholar : PubMed/NCBI
13	Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al: Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 373:1627–1639. 2015. View Article : Google Scholar : PubMed/NCBI
14	The Japan Lung Cancer Society: https://www.haigan.gr.jp/modules/guideline/index.php?content_id=3April 6–2018
15	Meropol NJ, Schrag D, Smith TJ, Mulvey TM, Langdon RM Jr, Blum D, Ubel PA and Schnipper LE; American Society of Clinical Oncology: American Society of Clinical Oncology guidance statement: The cost of cancer care. J Clin Oncol. 27:3868–3874. 2009. View Article : Google Scholar : PubMed/NCBI
16	Williams I, McIver S, Moore D and Bryan S: The use of economic evaluations in NHS decision-making: A review and empirical investigation. Health Technol Assess. 12(iii): ix–x, 1-175. 2008.
17	Ting J, Tien Ho P, Xiang P, Sugay A, Abdel-Sattar M and Wilson L: Cost-Effectiveness and Value of Information of Erlotinib, Afatinib, and Cisplatin-Pemetrexed for First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer in the United States. Value Health. 18:774–782. 2015. View Article : Google Scholar : PubMed/NCBI
18	Pharmaceutical Society: Insurance drug encyclopedia, Jiho. Pharmaceutical Society; Tokyo; 2012
19	Kawakami Y: Medical fee points table. 35th edition. Social Insurance Institute; Tokyo; 2008
20	US Department Of Health And Human Services: Common terminology criteria for adverse events (CTCAE) version 4.0. United States, National Cancer Institute. 2009, https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40April 6–2018
21	Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. 2013. View Article : Google Scholar : PubMed/NCBI
22	Shiroiwa T, Sung YK, Fukuda T, Lang HC, Bae SC and Tsutani K: International survey on willingness-to-pay (WTP) for one additional QALY gained: What is the threshold of cost effectiveness? Health Econ. 19:422–437. 2010. View Article : Google Scholar : PubMed/NCBI
23	Ohkusa Y and Sugawara T: Research for Willingness to Pay for One QALY Gain. Iryo To Shakai. 16:157–165. 2006.(In Japanese). View Article : Google Scholar
24	Takeda M, Okamoto I and Nakagawa K: Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 88:74–79. 2015. View Article : Google Scholar : PubMed/NCBI