BioltaLEE - New Data

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 tumor cell proliferation.
EJC March 07, 2023

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 (FI). 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 enrolled. Median follow-up was 26.9 months. High sTKa (>median) at baseline was associated with higher risk of progression (HR 2.21; 95% CI 1.45,3.37; P=0.0002); similar results were observed for patients with high sTKa levels at D15 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 vs. 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.