Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial

Currently, there are no clinically actionable biomarkers to predict patient to cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) plus endocrine therapy for hormone receptor (HR)[+]/ human epidermal growth factor receptor 2 (HER2)[-] advanced breast cancer (ABC). Herein, we report an exploratory...

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Detalles Bibliográficos
Autores: Albanell Mestres, Joan, Gamez-Pozo, Angelo, Arteaga, Carlos L., Bellet, Meritxell, Rojo, Federico, González, Abel, Bellosillo Paricio, Beatriz, Serra, Violeta, Gener, Petra, Guerrero, José A., Shimizu, Eileen, Mancino, Mario, Rodríguez-Morató, Jose, 1987-, Mina, Leonardo, Pérez-García, José Manuel, Cortés, Javier, Llombart-Cussac, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:dnet:rdupf_______::8e4d613db10af0dedf121044e1130233
Acceso en línea:https://hdl.handle.net/10230/73198
http://dx.doi.org/10.1038/s41523-025-00777-0
Access Level:acceso abierto
Palabra clave:Mama--Càncer
Marcadors bioquímics
Oncologia
Descripción
Sumario:Currently, there are no clinically actionable biomarkers to predict patient to cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) plus endocrine therapy for hormone receptor (HR)[+]/ human epidermal growth factor receptor 2 (HER2)[-] advanced breast cancer (ABC). Herein, we report an exploratory biomarker substudy (transFAL) from a subset of patients included in PARSIFAL, a phase II randomized clinical trial that evaluated first-line palbociclib plus fulvestrant or letrozole for HR[+]/HER2[-] ABC. No definitive biomarkers were discovered, however, worse outcomes were found with CDK6 postivity (p = 0.008), ER negativity (p = 0.008), high Ki67 (p = 0.04), and TP53 mutation (p = 0.04). ctDNA density (p = 0.036) and number of mutations (p = 0.033) at baseline were significantly higher for resistant patients. Our study reveals future directions to explore in the goal to determine biomarkers of response to CDK4/6i.