Data from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Year: 2024
Type: other
Abstract: Purpose: Giredestrant is an investigational next-generation, oral, selective estrogen receptor antagonist and degrader for the treatment of estrogen receptor–positive (ER+) breast cancer. We present the primary analysis results of the phase Ia/b GO39932 study (NCT03332797). Patients and Methods: Patients with ER+, HER2-negative locally advanced/metastatic breast cancer previously treated with endocrine therapy received single-agent giredestrant (10, 30, 90, or 250 mg), or giredestrant (100 mg) ± palbociclib 125 mg ± luteinizing hormone-releasing hormone (LHRH) agonist. Detailed cardiovascular assessment was conducted with giredestrant 100 mg. Endpoints included safety (primary), pharmacokinetics, pharmacodynamics, and efficacy. Results: As of January 28, 2021, with 175 patients enrolled, no dose-limiting toxicity was observed, and the MTD was not reached. Adverse events (AE) related to giredestrant occurred in 64.9% and 59.4% of patients in the single-agent ± LHRH agonist and giredestrant + palbociclib ± LHRH agonist cohorts, respectively (giredestrant-only–related grade 3/4 AEs were reported in 4.5% of patients across the single-agent cohorts and 3.1% of those with giredestrant + palbociclib). Dose-dependent asymptomatic bradycardia was observed, but no clinically significant changes in cardiac-related outcomes: heart rate, blood pressure, or exercise duration. Clinical benefit was observed in all cohorts (48.6% of patients in the single-agent cohort and 81.3% in the giredestrant + palbociclib ± LHRH agonist cohort), with no clear dose relationship, including in patients with ESR1-mutated tumors. Conclusions: Giredestrant was well tolerated and clinically active in patients who progressed on prior endocrine therapy. Results warrant further evaluation of giredestrant in randomized trials in early- and late-stage ER+ breast cancer.
Authors: Komal L. Jhaveri, Meritxell Bellet, Nicholas C. Turner, Sherene Loi, Aditya Bardia, Valentina Boni, Joohyuk Sohn, Tomas G. Neilan, Rafael Villanueva-Vázquez, Peter Kabos, Laura García-Estévez, Elena López-Miranda, J. Alejandro Pérez-Fidalgo, Jose M. Pérez-García, Jiajie Yu, Jill Fredrickson, Heather M. Moore, Ching-Wei Chang, John W. Bond, Jennifer Eng-Wong, Mary R. Gates, Elgene Lim
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Institute of Cancer Research, Royal Marsden Hospital, The University of Melbourne, Peter MacCallum Cancer Centre, Harvard University, Massachusetts General Hospital, Hospital Universitario Quirónsalud Madrid, HM Hospitales, Hospital Universitario HM Sanchinarro, IDCQ Hospitales y Sanidad, S.L.U., Yonsei University, Yonsei Cancer Hospital, Institut Català d'Oncologia, Duran i Reynals Hospital, University of Colorado Anschutz, MD Anderson Cancer Center Madrid, Hospital Universitario Ramón y Cajal, MedSIR (Spain), Hospital Clínico Universitario de Valencia, Genentech, Gilead Sciences (United States), Garvan Institute of Medical Research, UNSW Sydney
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4391910181