Eribulin: clinical review and new perspective in advanced breast cancer
Keywords:Eribulin, Mechanism of action, Metastatic breast cancer, Microtubule inhibitor, Triple-negative breast cancer
Eribulin is a unique microtubule inhibitor with mitotic and nonmitotic mechanisms of action. Eribulin has substantial activity in patients with pretreated (anthracycline and a taxane) advanced or metastatic breast cancer was confirmed by large-scale phase III clinical trials. We review recent pharmacological and clinical findings of eribulin use in metastatic breast cancer, particularly highlighting eribulin in difficult-to-treat and aggressive disease and safety data in specific patient populations. Furthermore, recent advancements and potential future directions for its clinical usage in our understanding are discussed. Ongoing studies of eribulin in combination with immunotherapies and established cytotoxic agents may facilitate to shape the future landscape in the treatment of breast cancer.
Worldwide cancer research fund. Fact sheet: worldwide cancer data, 2015. Available at: http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php. Accessed on 12 January 2021.
Mermer G, Turk M. Assessment of the effects of breast cancer training on women between the ages of 50 and 70 in Kemalpasa, Turkey. Asian Pac J Cancer Prev. 2014;15(24):10749-55.
Leśniczak B, Krasomski G, Oszukowski P, Stetkiewicz T, Woźniak P. Incidence of and mortality from breast cancer among women in Poland in the years 2001–2010. Prz Menopauzalny. 2014;13(6):344-7.
Ferrini K, Ghelfi F, Mannucci R, Titta L. Lifestyle, nutrition and breast cancer: facts and presumptions for consideration. Ecancermedicalscience. 2015;9:1-11.
Castelló A, Martín M, Ruiz A, Casas AM, Baena- Cañada JM, Lope V, et al. Lower breast cancer risk among women following the world cancer research fund and american institute for cancer research lifestyle recommendations: epigeicam case-control study. PLoS One. 2015;10(5):1-15.
Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clinic Canc Res. 2015;21(11):2445-52.
Garrone O, Miraglio E, Vandone AM, Vanella P, Lingua D, Merlano MC. Eribulin in advanced breast cancer: safety, efficacy and new perspectives. Future Oncol. 2017;13(30):2759-69.
Jordan M, Kamath K, Manna T, Okouneva T, Miller HP, Davis C. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005;4:1086‑95.
Shetty N, Gupta S. Eribulin drug review. South Asian J Cancer 2014;3(1):57-9.
Agoulnik SI, Kawano S, Taylor N, Oestreicher J, Matsui J, Chow J, et al. Eribulin mesylate exerts specific gene expression changes in pericytes and shortens pericyte-driven capillary network in vitro. Vasc cell. 2014;6(1):1.
Funahashi Y, Okamoto K, Adachi Y, Semba T, Uesugi M, Ozawa Y, et al. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci. 2014;105(10):1334-42.
Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer. 2014;110(6):1497-505.
O'Shaughnessy J, Kaklamani V, Kalinsky K. Perspectives on the mechanism of action and clinical application of eribulin for metastatic breast cancer. Future Oncol. 2019;15(14):1641-53.
Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001;61(3):1013-21.
Morgan RJ, Synold TW, Longmate JA, Quinn DI, Gandara D, Lenz HJ, et al. Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California cancer consortium trial. Cancer Chemother Pharmacol. 2015;76(5):897-907.
US FDA. Fact sheet: Highlights of prescribing information, 2010. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf. Accessed on 12 January 2021.
Zhang ZY, King BM, Pelletier RD, Wong YN. Delineation of the interactions between the chemotherapeutic agent eribulin mesylate (E7389) and human CYP3A4. Cancer Chemother Pharmacol. 2008;62(4):707-16.
Devriese LA, Witteveen PO, Marchetti S, Mergui-Roelvink M, Reyderman L, Wanders J, et al. Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairment. Cancer Chemotherap Pharmacol. 2012;70(6):823-32.
Tan AR, Sarantopoulos J, Lee L, Reyderman L, He Y, Olivo M, et al. Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function. Cancer Chemotherap Pharmacol. 2015;76(5):1051-61.
Kurebayashi J, Kanomata N, Yamashita T, Shimo T, Moriya T. Antitumor and anticancer stem cell activities of eribulin mesylate and antiestrogens in breast cancer cells. Breast Cancer. 2016;23(3):425-36.
David L, Luu TH, Xing Q, Han ES, Yip R, Yim JH. Effect of eribulin on cell growth and PI3K pathway activity with and without RAD001 in triple-negative and HER2-expressing breast cancer. J Clinic Oncol. 2013;31(26):173.
Tan AR, Rubin EH, Walton DC, Shuster DE, Wong YN, Fang F, et al. Phase 1 study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors. Clin Cancer Res. 2009;15(12):4213‑9.
Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001;61(3):1013‑21.
Aoqi K, Iwata H, Masuda N, Mukai H, Yoshida M, Rai Y, et al. A phase 2 study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2012;23(6):1441‑8.
Cortes J, Vahdat L, Blum JL, Twelves C, Campone M, Roché H, et al. Phase II Study of the Halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2010;28(25):3922‑8.
Vahdat LT, Pruitt B, Fabian CJ, Rivera RR, Smith DA, Tan‑Chiu E, et al. Phase II study of eribulin mesylate, A halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2009;27(18):2954‑61.
Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377(9769):914-23.
Muss H, Cortes J, Vahdat LT, Cardoso F, Twelves C, Yang J, et al. Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist. 2014;19(4):318.
Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33(6):594.
Twelves C, Cortes J, Vahdat L, Olivo M, He Y, Kaufman PA, et al. Efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of two phase 3 studies. Breast Cancer Res Treat. 2014;148(3):553-61.
Pivot X, Marmé F, Koenigsberg R, Guo M, Berrak E, Wolfer A. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncol. 2016;27(8):1525-31.
Barni S, Livraghi L, Morritti M, Vici P, Michelotti A, Cinieri S, et al. Eribulin in the treatment of advanced breast cancer: real-world scenario from 39 Italian centers–ESEMPiO study. Future Oncol. 2019;15(1):33-44.
Fabi A, Moscetti L, Ciccarese M, Caramanti M, Salesi N, Verde NL, et al. Eribulin in heavily pretreated metastatic breast cancer patients and clinical/biological feature correlations: impact on the practice. Future oncol. 2015;11(3):431-8.
Leo S, Arnoldi E, Repetto L, Coccorullo Z, Cinieri S, Fedele P, et al. Eribulin mesylate as third or subsequent line chemotherapy for elderly patients with locally recurrent or metastatic breast cancer: a multicentric observational study of GIOGer (Italian group of geriatric oncology)‐ERIBE. Oncologist. 2019;24(6):232.
Dranitsaris G, Gluck S, Faria C, Cox D, Rugo H. Comparative effectiveness analysis of monotherapy with cytotoxic agents in triple-negative metastatic breast cancer in a community setting. Clinical Therapeut. 2015;37(1):134-44.
Kish JK, Mougalian SS, Copher R, McAllister L, Zhixiao W, Broscious M. Abstract P5-15-16: Utilization and outcomes of eribulin in triple negative metastatic breast cancer: Real-world findings. Cancer Res. 2017:5-15.
Watanabe J. Eribulin monotherapy improved survivals in patients with ER-positive HER2-negative metastatic breast cancer in the real world: a single institutional review. Springerplus. 2015;4(1):1-6.
Wilks S, McIntyre K. Case studies in the management of metastatic breast cancer with eribulin. Clinic Med Insight: Oncol. 2015;9:27962.
Lorusso V, Cinieri S, Latorre A, Porcu L, Del-Mastro L, Puglisi F, et al. Efficacy and safety of eribulin in taxane-refractory patients in the ‘real world’. Future Oncol. 2017;13(11):971-8.
Matsuoka H, Tsurutani J, Tanizaki J, Iwasa T, Komoike Y, Koyama A, et al. Regression of brain metastases from breast cancer with eribulin: a case report. BMC Res. 2013;6(1):1-4.
Chang AY, Ying XX. Brain metastases from breast cancer and response to treatment with eribulin: a case series. Breast Cancer: Basic Clinic Res. 2015;9:21176.
Kish JK, Mougalian SS, Copher R, McAllister L, Wang Z, Janevski M, et al. Utilisation and outcomes of eribulin in triple-negative metastatic breast cancer (tn mbc): real-world findings. Asia Pac J Clinic Oncol. 2017;13:123-123.
Byun KD, Ahn SG, Baik HJ, Lee A, Bae KB, An MS, et al. Eribulin mesylate combined with local treatment for brain metastasis from breast cancer: two case reports. J Breast Canc. 2016;19(2):214.
Yoshinami T, Masuda N, Nakayama T, Hara F, Sagara Y, Kawaguchi H, et al. The utility of bi-weekly eribulin therapy for metastatic breast cancer: a Japanese multicenter Phase II study (JUST-STUDY). J. Clin. Oncol. 2015;33:1026.
Ohtani S, Nakayama T, Yoshinami T, Watanabe KI, Hara F, Sagara Y, et al. Bi-weekly eribulin therapy for metastatic breast cancer: a multicenter phase II prospective study (just-study). Breast Cancer. 2018;25(4):438-46.
Vahdat LT, Garcia AA, Vogel C, Pellegrino C, Lindquist DL, Iannotti N, et al. Eribulin mesylate versus ixabepilone in patients with metastatic breast cancer: a randomized Phase II study comparing the incidence of peripheral neuropathy. Breast Canc Res Treat. 2013;140(2):341-51.
Goel S, Mita AC, Mita M, Rowinsky EK, Chu QS, Wong N, et al. A phase I study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced solid malignancies. Clinic Cancer Res. 2009;15(12):4207-12.