Article (Scientific journals)
Landscape of baseline and acquired genomic alterations in circulating tumor DNA with abemaciclib alone or with endocrine therapy in advanced breast cancer.
Goetz, Matthew P; Hamilton, Erika P; Campone, Mario et al.
2023In Clinical Cancer Research
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Abstract :
[en] [en] PURPOSE: To identify potential predictors of response and resistance mechanisms in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with the CDK4/6 inhibitor abemaciclib +/- endocrine therapy (ET), baseline and acquired genomic alterations in circulating tumor DNA (ctDNA) were analyzed and associated with clinical outcomes. PATIENTS AND METHODS: MONARCH 3: postmenopausal women with HR+, HER2- ABC and no prior systemic therapy in the advanced setting were randomized 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 randomized 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.
Disciplines :
Oncology
Author, co-author :
Goetz, Matthew P ;  Mayo Clinic, Rochester, MN, United States
Hamilton, Erika P ;  Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee, United States
Campone, Mario ;  ICO, Saint-Herblain, France
Hurvitz, Sara A ;  Fred Hutchinson Cancer Center, Seattle, WA, United States
Cortes, Javier ;  International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain
Johnston, Stephen ;  Royal Marsden Hospital, London, United Kingdom
Llombart-Cussac, Antonio ;  Hospital Arnau de Vilanova, Valencia, Spain
Kaufman, Peter A ;  University of Vermont Cancer Center, Burlington, VT, United States
Toi, Masakazu ;  Kyoto University, Kyoto, Kyoto, Japan
Jerusalem, Guy  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Graham, Hillary ;  Eli Lilly and Company, Indianapolis, Indiana, United States
Wang, Hong ;  Eli Lilly and Company, United States
Jansen, Valerie M ;  Mersana Therapeutics, Cambridge, MA, United States
Litchfield, Lacey M ;  Eli Lilly and Company, Indianapolis, IN, United States
Martín, Miguel ;  Department of Medical Oncology, Hospital General Universitario Gregorio Marañón Instituto de Investigacion Sanitaria Gregorio Marañon, CIBERONC, Universidad Complutense, Madrid., Madrid, Spain
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Language :
English
Title :
Landscape of baseline and acquired genomic alterations in circulating tumor DNA with abemaciclib alone or with endocrine therapy in advanced breast cancer.
Publication date :
27 October 2023
Journal title :
Clinical Cancer Research
ISSN :
1078-0432
eISSN :
1557-3265
Publisher :
American Association for Cancer Research, Us pa
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 February 2024

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