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.

purposeIn 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

methodsTKa 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).

resultsIn the metastatic setting, TKa levels in baseline samples were inversely associated with the duration of PFS (hazard ratio, 1.91,

conclusionThese 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.