Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
Pharmacodynamics of Camizestrant Treatment in Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer: Results From the Randomized, Presurgical SERENA-3 Study.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Robertson John F R, Gogitidze Teimuraz, Katashvili Zaza, Rocha Juan Enrique Bargalló, Arkania Ekaterine, Moppett Iain, Cheung Kwok-Leung, Nemsadze Gia, Ajimi Maxine, Klinowska Teresa, Lindemann Justin P O, Mathewson Alastair, Morrow Christopher J, Nikolaou Myria, Scaltriti Maurizio, Sykes Andy, Dzagnidze Giorgi
Аннотация
PURPOSE: SERENA-3 is a presurgical window-of-opportunity (WOO) trial exploring the pharmacodynamic effects of camizestrant in postmenopausal women with newly diagnosed estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative breast cancer.
METHODS: This open-label, parallel-group trial randomly assigned 132 participants to receive camizestrant 75, 150, or 300 mg once daily for 5-7 days or 75 or 150 mg once daily for 12-15 days. The effects of camizestrant on ER expression, activity, and tumor proliferation were assessed in pre- and on-treatment tumor samples by immunohistochemical (IHC) analysis of ER, progesterone receptor (PgR), and Ki67. Exploratory analyses using transcriptomics and mass spectrometry were also performed.
RESULTS: ER expression was reduced by approximately 65% for all camizestrant doses, regardless of treatment duration. Reduction in Ki67 expression was greater after 12-15 days of camizestrant treatment, compared with 5-7 days. Exploratory analyses including mass spectrometry and IHC image analysis aligned with IHC H-score, indicating equivalent, maximal effects of all tested doses of camizestrant on ER expression and activity and Ki67 expression. Of those participants receiving camizestrant 75 mg once daily, 90%-100% reported no treatment-emergent adverse events across all preferred terms; of those reported, all were Grade 1 except one participant with Grade 2 upper respiratory tract infection, not considered related to camizestrant.
CONCLUSION: SERENA-3 demonstrates that camizestrant 75 mg once daily (Phase III dose) is well-tolerated and achieves maximal reduction in ER through known mechanisms, that is, antagonism and degradation, by 5-7 days, and proliferation suppression determined by Ki67 expression, by 12-15 days. These data support camizestrant 75 mg once daily as the preferred dose for ongoing clinical development and highlight the importance of presurgical WOO studies in guiding dose selection.
METHODS: This open-label, parallel-group trial randomly assigned 132 participants to receive camizestrant 75, 150, or 300 mg once daily for 5-7 days or 75 or 150 mg once daily for 12-15 days. The effects of camizestrant on ER expression, activity, and tumor proliferation were assessed in pre- and on-treatment tumor samples by immunohistochemical (IHC) analysis of ER, progesterone receptor (PgR), and Ki67. Exploratory analyses using transcriptomics and mass spectrometry were also performed.
RESULTS: ER expression was reduced by approximately 65% for all camizestrant doses, regardless of treatment duration. Reduction in Ki67 expression was greater after 12-15 days of camizestrant treatment, compared with 5-7 days. Exploratory analyses including mass spectrometry and IHC image analysis aligned with IHC H-score, indicating equivalent, maximal effects of all tested doses of camizestrant on ER expression and activity and Ki67 expression. Of those participants receiving camizestrant 75 mg once daily, 90%-100% reported no treatment-emergent adverse events across all preferred terms; of those reported, all were Grade 1 except one participant with Grade 2 upper respiratory tract infection, not considered related to camizestrant.
CONCLUSION: SERENA-3 demonstrates that camizestrant 75 mg once daily (Phase III dose) is well-tolerated and achieves maximal reduction in ER through known mechanisms, that is, antagonism and degradation, by 5-7 days, and proliferation suppression determined by Ki67 expression, by 12-15 days. These data support camizestrant 75 mg once daily as the preferred dose for ongoing clinical development and highlight the importance of presurgical WOO studies in guiding dose selection.