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Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review.
Gheysen, Mathilde; Punie, Kevin; Wildiers, Hans; Neven, Patrick.
Afiliación
  • Gheysen M; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: mathilde.gheysen@uzleuven.be.
  • Punie K; Department of General Medical Oncology, GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, 2610 Antwerpen, Belgium.
  • Wildiers H; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
  • Neven P; Department of Gynecology and Obstetrics and Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
Cancer Treat Rev ; 130: 102825, 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39293125
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancer Treat Rev Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancer Treat Rev Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos