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http://hdl.handle.net/2445/209921
Title: | 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: | Jhaveri, Komal L. Bellet, Meritxell Turner, Nicholas C. Loi, Sherene Bardia, Aditya Boni, Valentina Sohn, Joohyuk Neilan, Tomas G. Villanueva-vázquez, Rafael Kabos, Peter García-estévez, Laura López-miranda, Elena Pérez-fidalgo, J. Alejandro Pérez-garcía, Jose M. Yu, Jiajie Fredrickson, Jill Moore, Heather M. Chang, Ching-wei Bond, John W. Eng-wong, Jennifer Gates, Mary R. Lim, Elgene |
Issue Date: | 3-Nov-2023 |
Publisher: | American Association for Cancer Research (AACR) |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1158/1078-0432.CCR-23-1796 |
It is part of: | Clinical Cancer Research, 2023, vol. 30, issue. 4, p. 754-766 |
URI: | http://hdl.handle.net/2445/209921 |
Related resource: | https://doi.org/10.1158/1078-0432.CCR-23-1796 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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