Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer-Reference-Cited by-同舟云学术

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

Published:2024-01-23 Issue: Volume: Page:OF1-OF13
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Jhaveri Komal L.¹^ORCID,Bellet Meritxell²^ORCID,Turner Nicholas C.³^ORCID,Loi Sherene⁴^ORCID,Bardia Aditya⁵^ORCID,Boni Valentina⁶^ORCID,Sohn Joohyuk⁷^ORCID,Neilan Tomas G.⁸^ORCID,Villanueva-Vázquez Rafael⁹^ORCID,Kabos Peter¹⁰^ORCID,García-Estévez Laura¹¹^ORCID,López-Miranda Elena¹²^ORCID,Pérez-Fidalgo J. Alejandro¹³^ORCID,Pérez-García Jose M.¹⁴¹⁵,Yu Jiajie¹⁶^ORCID,Fredrickson Jill¹⁷^ORCID,Moore Heather M.¹⁸^ORCID,Chang Ching-Wei¹⁹^ORCID,Bond John W.²⁰^ORCID,Eng-Wong Jennifer¹⁷^ORCID,Gates Mary R.¹⁷^ORCID,Lim Elgene²¹^ORCID

Affiliation:

1. 1Department of Medicine, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York, and Weill Cornell Medical College, New York, New York.

2. 2Oncology Department, Breast Cancer Unit, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.

3. 3Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom.

4. 4Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, and The Sir Peter MacCallum Department of Medical Oncology, The University of Melbourne, Parkville, Australia.

5. 5Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

6. 6START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, HM Hospitales Sanchinarro, Madrid, Spain.

7. 7Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

8. 8Division of Cardiology, Department of Medicine, Cardio-Oncology Program, Massachusetts General Hospital, Boston, Massachusetts.

9. 9Institut Català d'Oncologia, l'Hospitalet–Hospital Duran i Reynals, Barcelona, Spain.

10. 10School of Medicine, University of Colorado, Aurora, Colorado.

11. 11Breast Cancer Department, MD Anderson Cancer Center Madrid, Madrid, Spain.

12. 12Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.

13. 13Hospital Clínico Universitario de Valencia, INCLIVA, CIBERONC, Valencia, Spain.

14. 14International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain.

15. 15Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain and Ridgewood, New Jersey.

16. 16Clinical Pharmacology, Genentech, Inc., South San Francisco, California.

17. 17Genentech Research and Early Development (gRED), Genentech, Inc., South San Francisco, California.

18. 18Oncology Biomarker Development, Genentech, Inc., South San Francisco, California.

19. 19PHC and Early Development Oncology Biostatistics, Genentech, Inc., South San Francisco, California.

20. 20Product Development Safety, Genentech, Inc., South San Francisco, California.

21. 21St. Vincent's Hospital and Garvan Institute of Medical Research, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

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). Experimental Design: 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 (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-23-1796/3380137/ccr-23-1796.pdf

Cited by 4 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer;Nature Reviews Clinical Oncology;2024-08-23

2. Selective Estrogen Receptor Degraders (SERDs);Current Breast Cancer Reports;2024-07-26

3. Mass Balance, Metabolic Pathways, Absolute Bioavailability, and Pharmacokinetics of Giredestrant in Healthy Subjects;Drug Metabolism and Disposition;2024-06-04

4. Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer;Cancer Research Communications;2023-12-15