Real-world second- and third-line progression-free survival after progression on first-line CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer by PAM50 intrinsic subtype: the SOLTI-1801 CDK-PREDICT study

Purpose: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated I...

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Detalles Bibliográficos
Autores: Tolosa, Pablo, Garcia Fructuoso, Isabel, Pascual, Tomás, Martínez-Sáez, Olga, Cejalvo Andújar, Juan Miguel, Servitja, Sonia, Fernández Abad, María, Benitez Fuentes, Javier David, Brasó-Maristany, Fara, Sanfeliu Torres, Esther, Lema, Laura, Ruano, Yolanda, Parrilla, Lucía, Roncero, Ana María, Cobos-Fernandez, Maria Angeles, Díaz, Irene, Centelles López, Karla Alicia, Sánchez Bayona, Rodrigo, Alva, Manuel, Madariaga, Ainhoa, Villacampa, Guillermo, Salvador, Fernando, Sánchez Belmonte, Agustín, Malumbres, Marcos, Prat Aparicio, Aleix, Ciruelos, Eva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:dnet:ubarcelona__::3753803c384ef449fa122c9711a89c26
Acceso en línea:https://hdl.handle.net/2445/229246
Access Level:acceso abierto
Palabra clave:Càncer de mama
Metabolisme
Marcadors bioquímics
Breast cancer
Metabolism
Biochemical markers
Descripción
Sumario:Purpose: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L). Methods: This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, CCNE1, PDCD1) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan-Meier and Cox models assessed associations with clinical, molecular, and treatment variables. Results: Among evaluable patients (n = 125 for rwPFS-2L; n = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2 months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86-2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07-13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3 months; HR 1.74; 95% CI 0.98-3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17-27.02). High CCNE1 expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02-1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS. Conclusions: Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.

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