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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Perspective

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer

Author(s): Surya K. De*

Volume 31, Issue 7, 2024

Published on: 15 June, 2023

Page: [791 - 795] Pages: 5

DOI: 10.2174/0929867330666230504152352

Abstract

Elacestrant was approved by the US FDA on January 27, 2023, for treating postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2- negative, ESR1-mutated advanced or metastatic breast cancer with disease progression prior to using at least one line of endocrine therapy. In this short perspective, physicochemical properties, dosage and administration, mechanism of action, pharmacodynamics, pharmacokinetics, drug interaction, and treatment-related adverse reactions of elacestrant are summarized.

Keywords: Selective estrogen receptor degraders, elacestrant, giredestrant, fulvestrant tamoxifen, endocrine therapy, estrogen receptor 1 gene.

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[1]
Bidard, F.C.; Kaklamani, V.G.; Neven, P.; Streich, G.; Montero, A.J.; Forget, F.; Mouret-Reynier, M.A.; Sohn, J.H.; Taylor, D.; Harnden, K.K.; Khong, H.; Kocsis, J.; Dalenc, F.; Dillon, P.M.; Babu, S.; Waters, S.; Deleu, I.; García Sáenz, J.A.; Bria, E.; Cazzaniga, M.; Lu, J.; Aftimos, P.; Cortés, J.; Liu, S.; Tonini, G.; Laurent, D.; Habboubi, N.; Conlan, M.G.; Bardia, A. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J. Clin. Oncol., 2022, 40(28), 3246-3256.
[http://dx.doi.org/10.1200/JCO.22.00338] [PMID: 35584336]
[2]
Wang, Y.; Tang, S.C. The race to develop oral SERDs and other novel estrogen receptor inhibitors: Recent clinical trial results and impact on treatment options. Cancer Metastasis Rev., 2022, 41(4), 975-990.
[http://dx.doi.org/10.1007/s10555-022-10066-y] [PMID: 36229710]
[3]
Lloyd, M.R.; Wander, S.A.; Hamilton, E.; Razavi, P.; Bardia, A. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: Current and emerging role. Ther. Adv. Med. Oncol., 2022, 14.
[http://dx.doi.org/10.1177/17588359221113694] [PMID: 35923930]
[4]
Bardia, A.; Kaklamani, V.; Wilks, S.; Weise, A.; Richards, D.; Harb, W.; Osborne, C.; Wesolowski, R.; Karuturi, M.; Conkling, P.; Bagley, R.G.; Wang, Y.; Conlan, M.G.; Kabos, P.; Phase, I. Phase I study of elacestrant (RAD1901), a novel selective estrogen receptor degrader, in ER-Positive, HER2-negative advanced breast cancer. J. Clin. Oncol., 2021, 39(12), 1360-1370.
[http://dx.doi.org/10.1200/JCO.20.02272] [PMID: 33513026]
[5]
Bihani, T.; Patel, H.K.; Arlt, H.; Tao, N.; Jiang, H.; Brown, J.L.; Purandare, D.M.; Hattersley, G.; Garner, F. Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), has antitumor activity in multiple ER+ breast cancer patient-derived xenograft models. Clin. Cancer Res., 2017, 23(16), 4793-4804.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2561] [PMID: 28473534]
[6]
Bardia, A.; Aftimos, P.; Bihani, T.; Anderson-Villaluz, A.T.; Jung, J.; Conlan, M.G.; Kaklamani, V.G. EMERALD: Phase III trial of elacestrant (RAD1901) vs. endocrine therapy for previously treated ER+ advanced breast cancer. Future Oncol., 2019, 15(28), 3209-3218.
[http://dx.doi.org/10.2217/fon-2019-0370] [PMID: 31426673]
[7]
Sanchez, K.G.; Nangia, J.R.; Schiff, R.; Rimawi, M.F. Elacestrant and the promise of oral SERDs. J. Clin. Oncol., 2022, 40(28), 3227-3229.
[http://dx.doi.org/10.1200/JCO.22.00841] [PMID: 35737918]
[8]
Jacobson, A. Elacestrant improves progression-free survival after endocrine therapy for estrogen receptor-positive metastatic breast cancer. Oncologist, 2022, 27(Suppl. 1), S7-S8.
[http://dx.doi.org/10.1093/oncolo/oyac015] [PMID: 35348779]
[9]
Conlan, M.G.; de Vries, E.F.J.; Glaudemans, A.W.J.M.; Wang, Y.; Troy, S. Pharmacokinetic and pharmacodynamic studies of elacestrant, a novel oral selective estrogen receptor degrader, in healthy post-menopausal women. Eur. J. Drug Metab. Pharmacokinet., 2020, 45(5), 675-689.
[http://dx.doi.org/10.1007/s13318-020-00635-3] [PMID: 32661909]
[10]
Wardell, S.E.; Nelson, E.R.; Chao, C.A.; Alley, H.M.; McDonnell, D.P. Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader. Endocr. Relat. Cancer, 2015, 22(5), 713-724.
[http://dx.doi.org/10.1530/ERC-15-0287] [PMID: 26162914]
[11]
Shah, N.; Mohammad, A.S.; Saralkar, P.; Sprowls, S.A.; Vickers, S.D.; John, D.; Tallman, R.M.; Lucke-Wold, B.P.; Jarrell, K.E.; Pinti, M.; Nolan, R.L.; Lockman, P.R. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol. Res., 2018, 132, 47-68.
[http://dx.doi.org/10.1016/j.phrs.2018.03.021] [PMID: 29604436]
[12]
Chinnasamy, K.; Saravanan, M.; Poomani, K. Investigation of binding mechanism and downregulation of elacestrant for wild and L536S mutant estrogen receptor‐α through molecular dynamics simulation and binding free energy analysis. J. Comput. Chem., 2020, 41(2), 97-109.
[http://dx.doi.org/10.1002/jcc.26076] [PMID: 31602686]
[13]
Patel, H.K.; Tao, N.; Lee, K.M.; Huerta, M.; Arlt, H.; Mullarkey, T.; Troy, S.; Arteaga, C.L.; Bihani, T. Elacestrant (RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors. Breast Cancer Res., 2019, 21(1), 146.
[http://dx.doi.org/10.1186/s13058-019-1230-0] [PMID: 31852484]
[14]
Lüftner, D. New treatment options for hormone receptor positive breast cancer in 2023. Curr. Opin. Obstet. Gynecol., 2023, 35(1), 62-66.
[http://dx.doi.org/10.1097/GCO.0000000000000834] [PMID: 36341983]
[15]
Garcia-Fructuoso, I.; Gomez-Bravo, R.; Schettini, F. Integrating new oral selective oestrogen receptor degraders in the breast cancer treatment. Curr. Opin. Oncol., 2022, 34(6), 635-642.
[http://dx.doi.org/10.1097/CCO.0000000000000892] [PMID: 36000362]
[16]
Liang, J.; Zbieg, J.R.; Blake, R.A.; Chang, J.H.; Daly, S.; DiPasquale, A.G.; Friedman, L.S.; Gelzleichter, T.; Gill, M.; Giltnane, J.M.; Goodacre, S.; Guan, J.; Hartman, S.J.; Ingalla, E.R.; Kategaya, L.; Kiefer, J.R.; Kleinheinz, T.; Labadie, S.S.; Lai, T.; Li, J.; Liao, J.; Liu, Z.; Mody, V.; McLean, N.; Metcalfe, C.; Nannini, M.A.; Oeh, J.; O’Rourke, M.G.; Ortwine, D.F.; Ran, Y.; Ray, N.C.; Roussel, F.; Sambrone, A.; Sampath, D.; Schutt, L.K.; Vinogradova, M.; Wai, J.; Wang, T.; Wertz, I.E.; White, J.R.; Yeap, S.K.; Young, A.; Zhang, B.; Zheng, X.; Zhou, W.; Zhong, Y.; Wang, X. GDC-9545 (Giredestrant): A potent and orally bioavailable selective estrogen receptor antagonist and degrader with an exceptional preclinical profile for er+ breast cancer. J. Med. Chem., 2021, 64(16), 11841-11856.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00847] [PMID: 34251202]
[17]
Hancock, G.R.; Young, K.S.; Hosfield, D.J.; Joiner, C.; Sullivan, E.A.; Yildiz, Y.; Lainé, M.; Greene, G.L.; Fanning, S.W. Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells. NPJ Breast Cancer, 2022, 8(1), 130.
[http://dx.doi.org/10.1038/s41523-022-00497-9] [PMID: 36517522]

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