Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor-Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial
Clin Cancer Res. 2021 Nov 15;27(22):6115-6123.
Study type
A multicenter (426 sites), prospective-retrospective translational medicine study, n = 454
Objective
To demonstrate that low serum Thymidine Kinase 1 (sTK1) activity (=TKa) (measured with the DiviTum®TKa test) is associated with low risk for disease progression and long PFS and OS. We assessed the prognostic effect of sTK1 (TKa) in patients with hormone receptor-positive metastatic breast cancer (MBC) treated in a prospective randomized SWOG trial of anastrozole (A) vs. A plus fulvestrant (A+F).
Background
Combination ET (endocrine therapy) or ET plus other targeted agents is associated with increased toxicities and costs compared to single agent ET. Thus, identification of patients who may not need combination therapy would serve to spare them these adverse events. Currently, there is no tool available to help clinicians tailor treatment for each patient, underlining the compelling need for identification of biomarkers of resistance and response to ET agents
Results
Patients with high versus low BL sTK1 (TKa) had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; P < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; P < 0.0001]. OS was significantly better for patients with high TKa who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; P = 0.0087]. Patients with low TKa had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low TKa had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, P < 0.0001, OS HR = 2.51, P < 0.0001]. Our results suggest that there are several potential practical applications for TKa in the care of patients with MBC.
Conclusion
The results of this translational medicine study suggest that BL sTK1 (TKa) identified patients with hormone receptor-positive MBC with a very favorable prognosis. Low BL TKa might identify patients who have indolent disease and may do well for a long time with first line ET alone and could safely be treated with ET monotherapy as upfront treatment for their metastatic disease. Delaying CDK4/6 or mTOR inhibitors might be warranted, decreasing toxicity and cost of therapy. Repetitive test-monitoring of TKa in MBC may allow early identification of patients whose tumors are resistant to therapy and who might benefit from switching to an alternative therapeutic strategy prior to detecting evidence of radiographic disease progression.
