Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study.

Autor:	Martín M; Hospital Gregorio Marañón, Universidad Complutense, GEICAM, CIBERONC, Madrid, Spain., Lim E; Garvan Institute of Medical Research, St Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia., Chavez-MacGregor M; The University of Texas MD Anderson Cancer Center, Houston, TX., Bardia A; Massachusetts General Hospital, Harvard Medical School, Boston, MA., Wu J; Fudan University Cancer Institute, Shanghai, China., Zhang Q; Harbin Medical University Cancer Hospital, Harbin, China., Nowecki Z; Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Cruz FM; Núcleo de Pesquisa e Ensino da Rede São Camilo, São Paulo, Brazil., Safin R; Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan, Kazan, Russian Federation., Kim SB; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Schem C; Krankenhaus Jerusalem, Mammazentrum Hamburg, Hamburg, Germany., Montero AJ; University Hospitals/Seidman Cancer Center, Case Western Reserve University, Cleveland, OH., Khan S; Nottingham University Hospitals, City Hospital Campus, Nottingham, United Kingdom., Bandyopadhyay R; Genentech, Inc, South San Francisco, CA., Moore HM; Genentech, Inc, South San Francisco, CA., Shivhare M; Roche Products Limited, Welwyn Garden City, United Kingdom., Patre M; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Martinalbo J; F. Hoffmann-La Roche Ltd, Basel, Switzerland.; Inhibrx, La Jolla, CA., Roncoroni L; F. Hoffmann-La Roche Ltd, Basel, Switzerland.; AstraZeneca, Barcelona, Spain., Pérez-Moreno PD; Genentech, Inc, South San Francisco, CA., Sohn J; Yonsei University College of Medicine, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Jun 20; Vol. 42 (18), pp. 2149-2160. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1200/JCO.23.01500
Abstrakt:	Purpose: To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455). Methods: Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). Results: At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1 m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1 m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. Conclusion: Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1 -mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.
Databáze:	MEDLINE
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