Transcriptomic Predictors of Survival for Palbociclib + Endocrine Therapy Versus Capecitabine in Aromatase Inhibitor–Resistant Breast Cancer From the GEICAM/2013-02 PEARL Trial

PURPOSEFor hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard of care. They are also used after progression on first-line aromatas...

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Detalles Bibliográficos
Autores: Agrawal, Yash N., Fernández Martínez, Aranzazu, Gil Gil, Miguel, Zielinski, Christoph, Ruiz Borrego, Manuel, Ciruelos, Eva, Muñoz Mateu, Montserrat, Margelí Vila, Mireia, Bermejo de las Heras, Begoña, Anton Torres, Antonio, Kahan, Zsuzsanna, Csöszi, Tibor, Alonso Romero, José Luis, García Saenz, José Ángel, Sánchez Rovira, Pedro, Álvarez, Elena, Chacón, José Ignacio, González Santiago, Santiago, Rodríguez Sánchez, César A., Servitja, Sonia, Pfefferle, Adam D., Herranz, Jesús, Liu, Yuan, Carey, Lisa A., Romero Camarero, Isabel, Caballero, Rosalía, Guerrero Zotano, Ángel, Perou, Charles M., Martín, Miguel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/222811
Acceso en línea:https://hdl.handle.net/2445/222811
Access Level:acceso abierto
Palabra clave:Càncer de mama
Tractament adjuvant del càncer
Breast cancer
Descripción
Sumario:PURPOSEFor hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard of care. They are also used after progression on first-line aromatase inhibitors (AIs), but some patients may respond better to chemotherapy-based options. We examined tumor features associated with survival from GEICAM/2013-02 PEARL, a phase III trial of palbociclib + ET versus capecitabine in AI-resistant HR+/HER2- MBC.METHODSFor 158 and 155 patients from each arm, 878 previously published gene expression signatures were derived using RNA sequencing on pretreatment tumor specimens, both primary and metastatic. Multivariable Cox models for progression-free survival (PFS) and overall survival (OS) were constructed with 16 preselected signatures related to proliferation, loss of retinoblastoma, and immune infiltration, and via Elastic Net using all signatures.RESULTSSignificant PFS difference by PAM50 intrinsic subtype was observed with palbociclib + ET. Comparing treatment arms, luminal A subtype trended toward longer PFS with palbociclib + ET, and luminal B and nonluminal subtypes had significantly longer PFS with capecitabine. Three B-cell (B-lymphocyte)-associated signatures correlated with shorter OS with palbociclib + ET. The immune-activated Immune1 TCGA breast cancer signature had significant treatment arm interaction for OS. Elastic Net iteratively selected B-cell-associated signatures independently associated with shorter OS with palbociclib + ET.CONCLUSIONPAM50 intrinsic subtype predicted PFS differences between palbociclib + ET and capecitabine. Lower B-cell-associated gene expression predicted longer OS with palbociclib + ET versus capecitabine. These features may help identify HR+/HER2- tumors resistant to further ET-based treatment with CDK4/6i.

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