dc.contributor.author | Jhaveri, KL | |
dc.contributor.author | Bellet, M | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Loi, S | |
dc.contributor.author | Bardia, A | |
dc.contributor.author | Boni, V | |
dc.contributor.author | Sohn, J | |
dc.contributor.author | Neilan, TG | |
dc.contributor.author | Villanueva-Vázquez, R | |
dc.contributor.author | Kabos, P | |
dc.contributor.author | García-Estévez, L | |
dc.contributor.author | López-Miranda, E | |
dc.contributor.author | Pérez-Fidalgo, JA | |
dc.contributor.author | Pérez-García, JM | |
dc.contributor.author | Yu, J | |
dc.contributor.author | Fredrickson, J | |
dc.contributor.author | Moore, HM | |
dc.contributor.author | Chang, C-W | |
dc.contributor.author | Bond, JW | |
dc.contributor.author | Eng-Wong, J | |
dc.contributor.author | Gates, MR | |
dc.contributor.author | Lim, E | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-01-30T10:38:40Z | |
dc.date.available | 2024-01-30T10:38:40Z | |
dc.date.issued | 2024-02-16 | |
dc.identifier | 730005 | |
dc.identifier.citation | Clinical Cancer Research, 2023, | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6135 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-23-1796 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-23-1796 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-10-31 | |
dc.date.updated | 2024-01-30T10:38:10Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-23-1796 | |
rioxxterms.licenseref.startdate | 2023-11-03 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37921755 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-23-1796 | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman on 2024-01-30. Deposit type is initial. No. of files: 1. Files: ccr-23-1796.pdf | |