JCO precision oncology · 2026
Real-World Plasma Thymidine Kinase Activity in High-Risk and Metastatic Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Treated With Cyclin-Dependent Kinase 4/6 Inhibitors.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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O'Connor Thomas N, Schultz Emily, Kabraji Sheheryar, Levine Ellis, Williams Amy J, Knudsen Erik S, Witkiewicz Agnieszka K
Аннотация
PURPOSE: In both the early and advanced settings, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for use in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) in combination with endocrine therapy and increase the duration of invasive disease-free survival and progression-free survival (PFS). The duration of response to these treatments is variable between individual patients, supporting the use of biomarkers to inform treatment. Here, we investigated plasma thymidine kinase activity (TKa) as a continuous prognostic and predictive biomarker of response to CDK4/6 inhibitor-based therapy in early and advanced hormone receptor-positive/HER2- BC.
MATERIALS AND METHODS: TKa levels were assessed longitudinally at baseline, on treatment, and post-treatment on plasma samples from 80 metastatic and 28 high-risk patients receiving CDK4/6 inhibitor-based therapy as the standard of care. Patients were enrolled in the prospective observational Roswell Park Ciclib Study (ClinicalTrials.gov identifier: NCT04526587).
RESULTS: In the metastatic setting, TKa levels in baseline samples were inversely associated with the duration of PFS (hazard ratio, 1.91, P = .03). There was also a reduction in TKa levels from baseline to on-treatment in metastatic disease that displayed longer PFS (≥20 months; 120.7 DiviTum units of activity, DuA v 30.6 DuA, P = .028). Individuals with metastatic disease that displayed shorter PFS (≤8 months) presented with higher TKa values on treatment (220.2 DuA v 30.6 DuA, P = .008) compared with patients with longer PFS. In early-stage high-risk cases, TKa values were lower on treatment compared with baseline (41.4 DuA v 114.8 DuA, P = 3.55e-08).
CONCLUSION: These findings support further investigation of circulating TKa levels as a continuous prognostic and predictive biomarker of response to CDK4/6 inhibitor-based therapy. Future studies are well-suited to assess definitive TKa cutoff values to inform treatment decisions.
MATERIALS AND METHODS: TKa levels were assessed longitudinally at baseline, on treatment, and post-treatment on plasma samples from 80 metastatic and 28 high-risk patients receiving CDK4/6 inhibitor-based therapy as the standard of care. Patients were enrolled in the prospective observational Roswell Park Ciclib Study (ClinicalTrials.gov identifier: NCT04526587).
RESULTS: In the metastatic setting, TKa levels in baseline samples were inversely associated with the duration of PFS (hazard ratio, 1.91, P = .03). There was also a reduction in TKa levels from baseline to on-treatment in metastatic disease that displayed longer PFS (≥20 months; 120.7 DiviTum units of activity, DuA v 30.6 DuA, P = .028). Individuals with metastatic disease that displayed shorter PFS (≤8 months) presented with higher TKa values on treatment (220.2 DuA v 30.6 DuA, P = .008) compared with patients with longer PFS. In early-stage high-risk cases, TKa values were lower on treatment compared with baseline (41.4 DuA v 114.8 DuA, P = 3.55e-08).
CONCLUSION: These findings support further investigation of circulating TKa levels as a continuous prognostic and predictive biomarker of response to CDK4/6 inhibitor-based therapy. Future studies are well-suited to assess definitive TKa cutoff values to inform treatment decisions.