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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Authors: 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
Format: article
Status:Published version
Publication Date:2026
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:dnet:ubarcelona__::3753803c384ef449fa122c9711a89c26
Online Access:https://hdl.handle.net/2445/229246
Access Level:Open access
Keyword:Càncer de mama
Metabolisme
Marcadors bioquímics
Breast cancer
Metabolism
Biochemical markers
Description
Summary: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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