Dynamic thymidine kinase activity independently captures treatment-specific biological response and is independently associated with outcomes in endocrine-resistant HR+ /HER2 − metastatic breast cancer: A translational analysis of the GEICAM/2013–02 PEARL trial
Guerrero-Zotano, Ángel ; Gil-Gil, Miguel ; Williams, Amy ; Ruiz-Borrego, Manuel ; Ritzén, Hanna ; Ciruelos, Eva María ; Muñoz, Montserrat ; Bermejo, Begoña ; Margelí, Mireia ; Antón, Antonio (Universidad de Zaragoza) ; Kahan, Zsuzsanna ; Csöszi, Tibor ; Alonso Murillo, Laura ; Murillo, Serafín Morales ; Lang, Istvan ; Rendo, Cristina Reboredo ; Alba, Emilio ; Álvarez, Pablo ; de la Haba-Rodriguez, Juan ; Álvarez, Isabel ; García, Andrés ; Herranz, Jesús ; Caballero, Rosalía ; Fisker, Helle ; Portela, Marta ; Rojo, Federico ; Martín, Miguel
Resumen: Background
Treatment selection in endocrine-resistant HR+ /HER2 − metastatic breast cancer (MBC) remains challenging, and early predictive biomarkers are lacking. Circulating thymidine kinase 1 activity (TKa) is a blood-based proliferation marker suitable for dynamic monitoring.
Methods
This translational study was conducted within the phase III GEICAM/2013–02 PEARL trial comparing endocrine therapy (ET) plus palbociclib versus capecitabine in HR+ /HER2 − MBC. Plasma from 555 patients was analyzed using a standardized FDA-cleared assay. TKa was assessed at baseline using a prespecified cutoff of 250 DuA to define low versus high proliferative activity, and additional thresholds were explored for treatment interaction and on-treatment monitoring. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using multivariable Cox models.
Results
Low baseline TKa (≤250 DuA) was independently associated with longer PFS (11.4 vs 4.0 months) and OS (38.5 vs 17.3 months), in multivariate analysis and irrespective of treatment. However, baseline TKa did not discriminate benefit between arms. Early on-treatment TKa dynamics provided treatment-specific information. At cycle 1 day 15, median TKa was higher with capecitabine than with ET plus palbociclib (448 vs 28 DuA), consistent with distinct mechanisms. In the capecitabine arm, a > 2-fold early increase in TKa was independently associated with improved PFS and OS. Conversely, persistently elevated TKa (>50 DuA) during ET plus palbociclib identified patients with poorer outcomes, regardless of baseline levels.
Conclusions
Baseline TKa is strongly prognostic, while early dynamic changes provide additional, treatment-specific information, reflecting differences in mechanism of action between therapies, that support response monitoring.
Idioma: Inglés
DOI: 10.1016/j.ejca.2026.116817
Año: 2026
Publicado en: European Journal of Cancer 242 (2026), 116817 [9 pp.]
ISSN: 0959-8049
Tipo y forma: Article (Published version)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material.
Exportado de SIDERAL (2026-06-03-11:04:59)
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Treatment selection in endocrine-resistant HR+ /HER2 − metastatic breast cancer (MBC) remains challenging, and early predictive biomarkers are lacking. Circulating thymidine kinase 1 activity (TKa) is a blood-based proliferation marker suitable for dynamic monitoring.
Methods
This translational study was conducted within the phase III GEICAM/2013–02 PEARL trial comparing endocrine therapy (ET) plus palbociclib versus capecitabine in HR+ /HER2 − MBC. Plasma from 555 patients was analyzed using a standardized FDA-cleared assay. TKa was assessed at baseline using a prespecified cutoff of 250 DuA to define low versus high proliferative activity, and additional thresholds were explored for treatment interaction and on-treatment monitoring. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using multivariable Cox models.
Results
Low baseline TKa (≤250 DuA) was independently associated with longer PFS (11.4 vs 4.0 months) and OS (38.5 vs 17.3 months), in multivariate analysis and irrespective of treatment. However, baseline TKa did not discriminate benefit between arms. Early on-treatment TKa dynamics provided treatment-specific information. At cycle 1 day 15, median TKa was higher with capecitabine than with ET plus palbociclib (448 vs 28 DuA), consistent with distinct mechanisms. In the capecitabine arm, a > 2-fold early increase in TKa was independently associated with improved PFS and OS. Conversely, persistently elevated TKa (>50 DuA) during ET plus palbociclib identified patients with poorer outcomes, regardless of baseline levels.
Conclusions
Baseline TKa is strongly prognostic, while early dynamic changes provide additional, treatment-specific information, reflecting differences in mechanism of action between therapies, that support response monitoring.
Idioma: Inglés
DOI: 10.1016/j.ejca.2026.116817
Año: 2026
Publicado en: European Journal of Cancer 242 (2026), 116817 [9 pp.]
ISSN: 0959-8049
Tipo y forma: Article (Published version)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material. Exportado de SIDERAL (2026-06-03-11:04:59)
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Record created 2026-06-03, last modified 2026-06-03