Phase Ia/b Study of Giredestrant &#177; Palbociclib and &#177; Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor-Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer

Jhaveri, KL; Bellet, M; Turner, NC; Loi, S; Bardia, A; Boni, V; Sohn, J; Neilan, TG; Villanueva-V&#225;zquez, R; Kabos, P; Garc&#237;a-Est&#233;vez, L; L&#243;pez-Miranda, E; P&#233;rez-Fidalgo, JA; P&#233;rez-Garc&#237;a, JM; Yu, J; Fredrickson, J; Moore, HM; Chang, CW; Bond, JW; Eng-Wong, J; Gates, MR; Lim, E

Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor-Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer

Author(s): Jhaveri, KL; Bellet, M; Turner, NC; Loi, S; Bardia, A; Boni, V; Sohn, J; Neilan, TG; Villanueva-Vázquez, R; Kabos, P; García-Estévez, L; López-Miranda, E; Pérez-Fidalgo, JA; Pérez-García, JM; Yu, J; Fredrickson, J; Moore, HM; Chang, CW; Bond, JW; Eng-Wong, J; Gates, MR; Lim, E;
Details: Publication Year 2024-02-16,Volume 30,Issue #4,Page 754-766
Journal Title: Clinical Cancer Research
Publication Type: Research article
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.
Publisher: American Association for Cancer Research
Keywords: Humans; Female; *Breast Neoplasms/drug therapy/genetics; Receptor, ErbB-2/genetics/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Receptors, Estrogen; Gonadotropin-Releasing Hormone/agonists; *Carbolines; *Piperazines; *Pyridines
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-23-1796
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-23-1796
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-12 06:47:05

Last Modified: 2024-03-12 06:47:25