Analysis of research on the benefits of clinical and economic effectiveness, safety of innovative drug cetuximab in the treatment of colorectal cancer

Authors

DOI:

https://doi.org/10.15587/2519-4852.2019.165681

Keywords:

cetuximab, colorectal cancer, clinical and economic efficiency, safety, epidermal growth factor receptor

Abstract

The aim of the work is to analyze and systematize literature data on the benefits of clinical and economic efficiency, safety of cetuximab in the treatment of colorectal cancer.

Materials and methods. Studies were conducted using databases on the Internet: PubMed; Food and Drug Administration, European Medicines Agency. It has used retrospective, logical, statistical and system-analytical research methods.

Results. The analysis of clinical data suggests additional utility, high efficacy of cetuximab in the treatment of patients with metastatic colorectal cancer RAS wild type and expression of epidermal growth factor receptors EGFR compared to other drugs. Cetuximab exhibits a synergistic effect with a number of cytostatic drugs, and also increases the effect of radiotherapy, with no increased toxic reactions when co-administered. The administration of cetuximab in the treatment regimen increases the resectability of primary nonresectable metastases in the liver, as well as survival without progression in both operated patients and in inoperable cases. The drug is considered relatively safe. Skin rashes caused by cetuximab are associated with a significant improvement in overall survival, progression-free survival and overall response rates. The use of cetuximab in patients with colorectal cancer is accompanied by a lower economic burden on the budget of drug provision for cancer patients than bevacizumab. It should be noted that the development of cetuximab biosimilars will reduce the cost of treatment and improve access to colorectal cancer therapy.

Conclusions. Thus, it has been shown that cetuximab is not only a clinically effective and relatively safe drug for the treatment of colorectal cancer, but also demonstrates its cost-effectiveness and additional benefits compared with other drugs, including bevacizumab

Author Biography

Elena Litvinova, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Sciences, Associate Professor

Department of Management and Economics of Enterprise

References

  1. Cancer prevention and control through an integrated approach (2017). Geneva: World Health Organization, Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA70-REC1/A70_2017_REC1-en.pdf
  2. Celis, J. E., Pavalkis, D. (2017). A mission-oriented approach to cancer in Europe: a joint mission/vision 2030. Molecular Oncology, 11 (12), 1661–1672. doi: http://doi.org/10.1002/1878-0261.12143
  3. Mach, J. P. (2017). Recombinant monoclonal antibodies, from tumor targetingto cancer immunotherapy, a critical overview. Molecular biology, 51 (6), 1024–1038. doi: http://doi.org/10.7868/s0026898417060131
  4. Kelly, R. J., Smith, T. J. (2014). Delivering maximum clinical benefit at an affordable price: engaging stakeholders in cancer care. The Lancet Oncology, 15 (3), e112–e118. doi: http://doi.org/10.1016/s1470-2045(13)70578-3
  5. Ferguson, J. S. J., Summerhayes, M., Masters, S., Schey, S., Smith, I. E. (2000). New treatments for advanced cancer: an approach to prioritization. British Journal of Cancer, 83 (10), 1268–1273. doi: http://doi.org/10.1054/bjoc.2000.1406
  6. Collins, M., Latimer, N. (2013). NICE’s end of life decision making scheme: impact on population health. BMJ, 346 (1), 1363–1363. doi: http://doi.org/10.1136/bmj.f1363
  7. Dilts, D. M. (2014). Time Has Come to Raise the Bar in Oncology Clinical Trials. Journal of Clinical Oncology, 32 (12), 1186–1187. doi: http://doi.org/10.1200/jco.2013.54.5277
  8. Polyakova, D. (2019). Half of the new drugs does not carry additional benefits. Weekly Pharmacy, 1174 (3). Available at: https://www.apteka.ua/article/487540
  9. Sobrero, A. F., Maurel, J., Fehrenbacher, L., Scheithauer, W., Abubakr, Y. A., Lutz, M. P. et. al. (2008). EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal Cancer. Journal of Clinical Oncology, 26 (14), 2311–2319. doi: http://doi.org/10.1200/jco.2007.13.1193
  10. Cutsem, E. Van, Nowacki, M., Lang, I., Cascinu, S., Shchepotin, I. et. al. (2007). Randomized phase III study of irinotecan and 5FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer. CRYSTAL trial. Journal of Clinical Oncology, 25 (18), 164.
  11. Van Cutsem, E., Köhne, C.-H., Láng, I., Folprecht, G., Nowacki, M. P., Cascinu, S. et. al. (2011). Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status. Journal of Clinical Oncology, 29 (15), 2011–2019. doi: http://doi.org/10.1200/jco.2010.33.5091
  12. Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A. et. al. (2004). Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. New England Journal of Medicine, 351 (4), 337–345. doi: http://doi.org/10.1056/nejmoa033025
  13. Heinemann, V., von Weikersthal, L. F., Vehling-Kaiser, U., Stauch, M., Oruzio, D., Schulze, M. et. al. (2008). Randomized trial comparing cetuximab plus XELIRI versus cetuximab plus XELOX as first line treatment of patients with metastatic colorectal cancer (mCRC): A study of the german AIO CRC study group. Journal of Clinical Oncology, 26 (15), 4033–4033. doi: http://doi.org/10.1200/jco.2008.26.15_suppl.4033
  14. Wasan, H., Adams, R. A., Wilson, R. H., Pugh, C., Fisher, D., Madi, A. et. al. (2012). Intermittent chemotherapy (CT) plus continuous or intermittent cetuximab (C) in the first-line treatment of advanced colorectal cancer (aCRC): Results of the two-arm phase II randomized MRC COIN-B trial. Journal of Clinical Oncology, 30 (4), 536–536. doi: http://doi.org/10.1200/jco.2012.30.4_suppl.536
  15. Ye, L.-C., Liu, T.-S., Ren, L., Wei, Y., Zhu, D.-X., Zai, S.-Y. et. al. (2013). Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients WithKRASWild-Type Unresectable Colorectal Liver-Limited Metastases. Journal of Clinical Oncology, 31 (16), 1931–1938. doi: http://doi.org/10.1200/jco.2012.44.8308
  16. Osumi, H., Shinozaki, E., Mashima, T., Wakatsuki, T., Suenaga, M., Ichimura, T. et. al. (2018). Phase II trial of biweekly cetuximab and irinotecan as third-line therapy for pretreated KRAS exon 2 wild-type colorectal cancer. Cancer Science, 109 (8), 2567–2575. doi: http://doi.org/10.1111/cas.13698
  17. Cheng, A.-L., Cornelio, G., Shen, L., Price, T., Yang, T.-S., Chung, I. J. et. al. (2017). Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study. Clinical Colorectal Cancer, 16 (2), e73–e88. doi: http://doi.org/10.1016/j.clcc.2016.08.005
  18. Pietrantonio, F., Di Bartolomeo, M., Cotsoglou, C., Mennitto, A., Berenato, R., Morano, F. et. al. (2017). Perioperative Triplet Chemotherapy and Cetuximab in Patients With RAS Wild Type High Recurrence Risk or Borderline Resectable Colorectal Cancer Liver Metastases. Clinical Colorectal Cancer, 16 (3), e191–e198. doi: http://doi.org/10.1016/j.clcc.2016.09.007
  19. Stintzing, S., Miller-Phillips, L., Modest, D. P., Fischer von Weikersthal, L., Decker, T., Kiani, A. et. al. (2017). Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study. European Journal of Cancer, 79, 50–60. doi: http://doi.org/10.1016/j.ejca.2017.03.023
  20. Lévi, F., Karaboué, A., Saffroy, R., Desterke, C., Boige, V., Smith, D. et. al. (2017). Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228). British Journal of Cancer, 117 (7), 965–973. doi: http://doi.org/10.1038/bjc.2017.278
  21. Van Geel, R. M. J. M., Tabernero, J., Elez, E., Bendell, J. C., Spreafico, A., Schuler, M. et. al. (2017). A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer. Cancer Discovery, 7 (6), 610–619. doi: http://doi.org/10.1158/2159-8290.cd-16-0795
  22. Sunakawa, Y., Ichikawa, W., Tsuji, A., Denda, T., Segawa, Y., Negoro, Y. Et. al. (2017). Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials. Clinical Colorectal Cancer, 16 (3), e171–e180. doi: http://doi.org/10.1016/j.clcc.2016.09.010
  23. Ciardiello, F., Normanno, N., Martinelli, E., Troiani, T., Pisconti, S., Cardone, C. et. al. (2016). Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX. Annals of Oncology, 27 (6), 1055–1061. doi: http://doi.org/10.1093/annonc/mdw136
  24. Nakamura, M., Aoyama, T., Ishibashi, K., Tsuji, A., Takinishi, Y., Shindo, Y. (2016). Randomized phase II study of cetuximab versus irinotecan and cetuximab in patients with chemo-refractory KRAS codon G13D metastatic colorectal cancer (G13D-study). Cancer Chemotherapy and Pharmacology, 79 (1), 29–36. doi: http://doi.org/10.1007/s00280-016-3203-7
  25. Stintzing, S., Modest, D. P., Rossius, L., Lerch, M. M., von Weikersthal, L. F., Decker, T. et. al. (2016). FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. The Lancet Oncology, 17 (10), 1426–1434. doi: http://doi.org/10.1016/s1470-2045(16)30269-8
  26. Liu, G., Tu, D., Lewis, M., Cheng, D., Sullivan, L. A., Chen, Z. et. al. (2016). Fc- Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer. Clinical Cancer Research, 22 (10), 2435–2444. doi: http://doi.org/10.1158/1078-0432.ccr-15-0414
  27. Hazama, S., Maeda, H., Iwamoto, S., Kim, H. M., Takemoto, H., Kobayashi, K. et. al. (2016). A Phase II Study of XELOX and Cetuximab as First-Line Therapy in Patients With KRAS Wild Type Metastatic Colorectal Cancer (FLEET2 Study). Clinical Colorectal Cancer, 15 (4), 329–336. doi: http://doi.org/10.1016/j.clcc.2016.07.003
  28. Takahashi, T., Emi, Y., Oki, E., Kobayashi, K., Tsuji, A. et. al. (2016). Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study). Cancer Chemotherapy and Pharmacology, 78 (3), 585–593. doi: http://doi.org/10.1007/s00280-016-3109-4
  29. Terazawa, T., Nishitani, H., Kato, K., Hashimoto, H., Akiyoshi, K., Ito, Y. (2015). Phase II study of cetuximab with irinotecan for KRAS wild-type colorectal cancer in Japanese patients. Asia-Pacific Journal of Clinical Oncology, 13 (2), e132–e137. doi: http://doi.org/10.1111/ajco.12405
  30. Folprecht, G., Gruenberger, T., Bechstein, W., Raab, H.-R., Weitz, J., Lordick, F. et. al. (2014). Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study)†. Annals of Oncology, 25 (5), 1018–1025. doi: http://doi.org/10.1093/annonc/mdu088
  31. Abdel-Rahman, O., Fouad, M. (2015). Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 93 (2), 127–135. doi: http://doi.org/10.1016/j.critrevonc.2014.07.005
  32. Petrelli, F., Ardito, R., Ghidini, A., Zaniboni, A., Ghidini, M., Barni, S., Tomasello, G. (2018). Different Toxicity of Cetuximab and Panitumumab in Metastatic Colorectal Cancer Treatment: A Systematic Review and Meta-Analysis. Oncology, 94 (4), 191–199. doi: http://doi.org/10.1159/000486338
  33. Jiang, W., Yu, Q., Ning, R., Zhao, W., Wei, C. (2018). Efficacy of bevacizumab versus epidermal growth factor receptor inhibitors for wild-type RAS metastatic colorectal cancer: a meta-analysis. OncoTargets and Therapy, 11, 4271–4281. doi: http://doi.org/10.2147/ott.s168695
  34. Cao, D.-D., Xu, H.-L., Xu, X.-M., Ge, W. (2017). The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis. Oncotarget, 8 (32), 53631–53641. doi: http://doi.org/10.18632/oncotarget.19022
  35. Yang, Y.-F., Wang, G.-Y., He, J.-L., Wu, F.-P., Zhang, Y.-N. (2017). Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer. Medicine, 96 (12), e6335. doi: http://doi.org/10.1097/md.0000000000006335
  36. Shankaran, V., Ortendahl, J. D., Purdum, A. G., Bolinder, B., Anene, A. M., Sun, G. H., Bentley, T. G. K. (2015). Cost-Effectiveness of Cetuximab as First-line Treatment for Metastatic Colorectal Cancer in the United States. American Journal of Clinical Oncology, 41 (1), 65–72. doi: http://doi.org/10.1097/coc.0000000000000231

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Published

2019-04-30

How to Cite

Litvinova, E. (2019). Analysis of research on the benefits of clinical and economic effectiveness, safety of innovative drug cetuximab in the treatment of colorectal cancer. ScienceRise: Pharmaceutical Science, (2 (18), 22–27. https://doi.org/10.15587/2519-4852.2019.165681

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Pharmaceutical Science