Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial.
Humans
Female
Breast Neoplasms
/ pathology
Letrozole
/ therapeutic use
Proportional Hazards Models
Thymidine Kinase
/ therapeutic use
Prospective Studies
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Aminopyridines
/ therapeutic use
Aromatase Inhibitors
/ therapeutic use
Biomarkers
Receptor, ErbB-2
/ metabolism
Advanced breast cancer
Biomarker
Letrozole
Ribociclib
Thymidine kinase
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
02
12
2022
revised:
28
02
2023
accepted:
01
03
2023
medline:
19
5
2023
pubmed:
2
4
2023
entrez:
1
4
2023
Statut:
ppublish
Résumé
Thymidine kinase 1 (TK1) is an enzyme downstream of the CDK4/6 pathway, with a critical role in DNA synthesis; serum TK1 activity (sTKa) is a novel liquid biopsy biomarker of tumour cell proliferation. The phase IIIb, BioItaLEE trial (NCT03439046) collected sera from postmenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib plus letrozole at baseline, day 15 of cycle 1 (C1D15), day 1 of cycle 2 (C2D1), and at first imaging. Associations between sTKa assessed at different time points or sTKa dynamic patterns, and progression-free survival (PFS) were evaluated using multivariate Cox models. Overall, 287 patients were enroled. Median follow-up was 26.9 months. High sTKa (>median) at baseline was associated with higher risk of progression (hazard ratio [HR], 2.21; 95% confidence interval [95% CI], 1.45, 3.37; P = 0.0002); similar results were observed for patients with high sTKa levels at C1D15 and C2D1. Early sTKa dynamic patterns were strongly predictive of PFS. The pattern with high sTKa levels at C2D1 following initial decrease at C1D15 was associated with higher risk of progression versus the pattern with low sTKa levels at both time points (HR, 2.89; 95% CI, 1.57, 5.31; P = 0.0006), while the pattern with high sTKa levels at C1D15 was associated with the shortest PFS (HR, 5.65; CI: 2.84, 11.2; P < 0.0001). Baseline and dynamic sTKa changes provided independent information. sTKa appears to be a new promising prognostic and pharmacodynamic biomarker in patients with HR+/HER2- ABC treated with ribociclib plus letrozole as first-line therapy.
Sections du résumé
BACKGROUND
Thymidine kinase 1 (TK1) is an enzyme downstream of the CDK4/6 pathway, with a critical role in DNA synthesis; serum TK1 activity (sTKa) is a novel liquid biopsy biomarker of tumour cell proliferation.
METHODS
The phase IIIb, BioItaLEE trial (NCT03439046) collected sera from postmenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib plus letrozole at baseline, day 15 of cycle 1 (C1D15), day 1 of cycle 2 (C2D1), and at first imaging. Associations between sTKa assessed at different time points or sTKa dynamic patterns, and progression-free survival (PFS) were evaluated using multivariate Cox models.
RESULTS
Overall, 287 patients were enroled. Median follow-up was 26.9 months. High sTKa (>median) at baseline was associated with higher risk of progression (hazard ratio [HR], 2.21; 95% confidence interval [95% CI], 1.45, 3.37; P = 0.0002); similar results were observed for patients with high sTKa levels at C1D15 and C2D1. Early sTKa dynamic patterns were strongly predictive of PFS. The pattern with high sTKa levels at C2D1 following initial decrease at C1D15 was associated with higher risk of progression versus the pattern with low sTKa levels at both time points (HR, 2.89; 95% CI, 1.57, 5.31; P = 0.0006), while the pattern with high sTKa levels at C1D15 was associated with the shortest PFS (HR, 5.65; CI: 2.84, 11.2; P < 0.0001). Baseline and dynamic sTKa changes provided independent information.
CONCLUSIONS
sTKa appears to be a new promising prognostic and pharmacodynamic biomarker in patients with HR+/HER2- ABC treated with ribociclib plus letrozole as first-line therapy.
Identifiants
pubmed: 37003098
pii: S0959-8049(23)00119-3
doi: 10.1016/j.ejca.2023.03.001
pii:
doi:
Substances chimiques
Letrozole
7LKK855W8I
ribociclib
TK8ERE8P56
Thymidine Kinase
EC 2.7.1.21
Aminopyridines
0
Aromatase Inhibitors
0
Biomarkers
0
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Clinical Trial, Phase III
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-11Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.