دورية أكاديمية
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
| العنوان: | The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer |
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| المؤلفون: | Mayer, Ingrid, Winer, Eric, Linden, Hannah, Ma, Cynthia X., Parker, Barbara A., Bellet Ezquerra, Meritxell, Bardia, Aditya |
| المساهمون: | Institut Català de la Salut, Bardia A Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. Mayer I Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. AstraZeneca, Gaithersburg, MD, USA. Winer E Dana-Farber Cancer Institute, Boston, MA, USA. Yale Cancer Center, New Haven, CT, USA. Linden HM University of Washington, Seattle, WA, USA. Ma CX Washington University School of Medicine, St. Louis, MO, USA. Parker BA University of California San Diego Moores Cancer Center, San Diego, CA, USA. Bellet M Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Springer |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Estrògens - Antagonistes - Ús terapèutic, Menopausa, Mama - Càncer - Tractament, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms, Other subheadings::Other subheadings::Other subheadings::/drug therapy, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormone Antagonists::Estrogen Antagonists, Other subheadings::Other subheadings::/therapeutic use, PHENOMENA AND PROCESSES::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::hormonas, sustitutos de hormonas y antagonistas de hormonas::antagonistas de hormonas::antagonistas de estrógenos, Otros calificadores::Otros calificadores::/uso terapéutico, FENÓMENOS Y PROCESOS::fenómenos fisiológicos reproductivos y urinarios::fenómenos fisiológicos de la reproducción::climaterio::menopausia::posmenopausia |
| الوصف: | Metastatic breast cancer; Postmenopausal ; Càncer de mama metastàtic; Postmenopausa ; Cáncer de mama metastásico; Postmenopausia ; Purpose GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling. Methods A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 −) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status. Results Patients (N = 152) received GDC-0810 100–800 mg once daily (QD) or 300–400 mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600 mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (> 90%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring ESR1 mutations included partial responses (4% overall; 4% ESR1), stable disease (39% overall; 42% ESR1), non-complete response/non-progressive disease (13% overall; 12% ESR1), progressive disease (40% overall; 38% ESR1), and missing/unevaluable (5% overall; 5% ESR1). Clinical benefit (responses or SD, lasting ≥ 24 weeks) was observed in patients in dose escalation (n = 16, 39%) and expansion (n = 24, 22%). Conclusion GDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER + advanced/MBC, with/without ESR1 mutations, highlighting the potential for oral SERDs. ; This work was ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1573-7217 |
| العلاقة: | Breast Cancer Research and Treatment;197; https://doi.org/10.1007/s10549-022-06797-9Test; Bardia A, Mayer I, Winer E, Linden HM, Ma CX, Parker BA, et al. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer. Breast Cancer Res Treat. 2023 Jan;197:319–31.; https://hdl.handle.net/11351/9315Test; 000885413200001 |
| DOI: | 10.1007/s10549-022-06797-9 |
| الإتاحة: | https://doi.org/10.1007/s10549-022-06797-9Test https://hdl.handle.net/11351/9315Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.79338F71 |
| قاعدة البيانات: | BASE |
| تدمد: | 15737217 |
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| DOI: | 10.1007/s10549-022-06797-9 |