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

PurposeEstrogen 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...

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Detalles Bibliográficos
Autores: Tolosa, P, García-Fructuoso, I, Pascual, T, Martínez-Sáez, O, Cejalvo, JM, Servitja, S, Abad, MF, Fuentes, JDB, Brasó-Maristany, F, Sanfeliu, E, Lema, L, Ruano, Y, Parrilla, L, Roncero, AM, Cobos, MA, Díaz, I, López, KAC, Sánchez-Bayona, R, Alva, M, Madariaga, A, Villacampa, G, Salvador, F, Sánchez-Belmonte, A, Malumbres, M, Prat, A, Ciruelos, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:dnet:incliva_____::e33f37cf6aba1956135489401866c8a2
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/20881
Access Level:acceso abierto
Palabra clave:CDK 4/6 inhibitors
Hormone receptor-positive/HER2-negative advanced breast cancer
PAM50
Intrinsic subtypes
rwPFS-2L
SERDs
PI3K inhibitors
Descripción
Sumario:PurposeEstrogen 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).MethodsThis 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.ResultsAmong 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.ConclusionsOutcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.

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