Presurgical window-of-opportunity study of pharmacodynamics of camizestrant for postmenopausal ER-positive, HER2-negative primary breast cancer

SERENA-3 is a multinational presurgical window-of-opportunity trial exploring the pharmacodynamic effects of camizestrant in postmenopausal women with newly diagnosed ER-positive, HER2-negative breast cancer. This parallel-group trial randomly assigend 132 participants to receive camizestrant 75, 150, or 300 mg once daily for 5-7 days or 75 or 150 m once daily for 12-15 days. 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. No serious adverse events were reported. The authors conclude that SERENA-3 demonstrateds 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 by 12-15 days.