Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review.

BACKGROUND

Primary and acquired endocrine resistance remains a major issue in the treatment of hormone receptor positive breast cancer. Acquired resistance often results from estrogen receptor 1 (ESR1) mutations leading to estrogen independent estrogen receptor activation. Selective estrogen receptor degraders (SERDs) induce degradation of this receptor, thereby overcoming this resistance. The intramuscular administration and modest efficacy of fulvestrant, the first SERD, triggered development of oral, more potent SERDs. This narrative review gives an overview of the current evidence regarding this new drug class.

METHODS

Medline/PubMed and Embase database were screened using a systematic search strategy. We assessed the San Antonio Breast Cancer Symposium abstract reports, the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meeting resources by applying the following terms: 'SERD', 'giredestrant', 'elacestrant', 'imlunestrant', 'amcenestrant', 'camizestrant' and 'rintodestrant'.

CLINICALTRIALS

gov was consulted to include ongoing trials.

RESULTS

The search retrieved 1191 articles. After screening, 108 articles were retained. In the phase 3 EMERALD trial, elacestrant demonstrated benefit in progression free survival (PFS) in second line metastatic disease in postmenopausal women or men, leading to Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the ESR1 mutated population. This PFS advantage was more pronounced among patients who had priorly received at least 12 months of a cyclin-dependent kinases 4/6 inhibitor (CDK4/6i). In the phase 2 SERENA-2 trial, camizestrant improved PFS as second line treatment. However, trials of giredestrant and amcenestrant failed to show PFS benefit in second line metastatic setting. In the preoperative setting, several oral SERDs resulted in a significant reduction of tumoral proliferation. Furthermore, many trials are still in progress.

CONCLUSION

Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [For Dr. Mathilde Gheysen: no conflicts of interest. For Dr. Kevin Punie: his institute received research grants from MSD and Sanofi. He received speaker fees and honoraria for consultancy and advisory board functions from Astra Zeneca, Eli Lilly, Exact Sciences, Focus Patient, Gilead, Medimix, MSD, Novartis, Pfizer, Roche, Sanofi, Seagen. He also received speaker fees and honoraria for consultancy and advisory board functions to institution: Astra Zeneca, Eli Lilly, Exact Sciences, Gilead, MSD, Novartis, Pfizer, Roche, Seagen. Travel grants from Astra Zeneca, Gilead, Novartis, Pfizer, PharmaMar, Roche. For Prof. Dr. Patrick Neven: in the last 12 months, his institution received fees for his activities in consultancy (Pfizer, Novartis, Eli Lilly, Roche, Astrazeneca), in advisory Boards (Astrazeneca, Pfizer, Novartis, Lilly, Roche, Medscape, Gilead, Menarini) and lecturing & attendance at scientific exchange meetings. For Prof. Dr. Hans Wildiers: his institution received financial compensation on his behalf for advisory boards, lecture fees and/or consultancy fees from Daiichi Sankyo, Gilead, Lilly, Pfizer, Novartis, MSD, Relay Therapeutics, PSI, Augustine Therapeutics, Astra Zeneca, Roche. He received travel support from Gilead, Daiichi Sankyo, Pfizer].