Landscape of Baseline and Acquired Genomic Alterations in Circulating Tumor DNA with Abemaciclib Alone or with Endocrine Therapy in Advanced Breast Cancer.

Autor:	Goetz MP; Mayo Clinic, Rochester, Minnesota., Hamilton EP; Sarah Cannon Research Institute, Tennessee Oncology PLCC, Nashville, Tennessee., Campone M; Institut de Cancerologie de l'Ouest, Angers Cedex, France., Hurvitz SA; University of California, Los Angeles, California., Cortes J; Oncology Department, International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain.; Department of Medicine, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Madrid, Spain., Johnston S; The Royal Marsden NHS Foundation Trust, London, United Kingdom., Llombart-Cussac A; Hospital Arnau Vilanova, Valencia, Spain., Kaufman PA; University of Vermont Medical Center, Burlington, Vermont., Toi M; Kyoto University, Kyoto, Japan., Jerusalem G; CHU Liege and Liege University, Liege, Belgium., Graham H; Eli Lilly and Company, Indianapolis, Indiana., Wang H; Eli Lilly and Company, Indianapolis, Indiana., Jansen VM; Eli Lilly and Company, Indianapolis, Indiana., Litchfield LM; Eli Lilly and Company, Indianapolis, Indiana., Martin M; Instiuto de Investigacion Santaria Gregorio Maranon, Universidad Complutense, CIBERONC, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 May 15; Vol. 30 (10), pp. 2233-2244.
DOI:	10.1158/1078-0432.CCR-22-3573
Abstrakt:	Purpose: To identify potential predictors of response and resistance mechanisms in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) treated with the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib ± endocrine therapy (ET), baseline and acquired genomic alterations in circulating tumor DNA (ctDNA) were analyzed and associated with clinical outcomes. Experimental Design: MONARCH 3: postmenopausal women with HR+, HER2- ABC and no prior systemic therapy in the advanced setting were randomly assigned to abemaciclib or placebo plus nonsteroidal aromatase inhibitor (NSAI). nextMONARCH: women with HR+, HER2- metastatic breast cancer that progressed on/after prior ET and chemotherapy were randomly assigned to abemaciclib alone (two doses) or plus tamoxifen. Baseline and end-of-treatment plasma samples from patients in MONARCH 3 and nextMONARCH (monotherapy arms) were analyzed to identify somatic genomic alterations. Association between genomic alterations and median progression-free survival (mPFS) was assessed. Results: Most patients had ≥1 genomic alteration detected in baseline ctDNA. In MONARCH 3, abemaciclib+NSAI was associated with improved mPFS versus placebo+NSAI, regardless of baseline alterations. ESR1 alterations were less frequently acquired in the abemaciclib+NSAI arm than placebo+NSAI. Acquired alterations potentially associated with resistance to abemaciclib ± NSAI included RB1 and MYC. Conclusions: In MONARCH 3, certain baseline ctDNA genomic alterations were prognostic for ET but not predictive of abemaciclib response. Further studies are warranted to assess whether ctDNA alterations acquired during abemaciclib treatment differ from other CDK4/6 inhibitors. Findings are hypothesis generating; further exploration is warranted into mechanisms of resistance to abemaciclib and ET. See related commentary by Wander and Bardia, p. 2008. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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