Journal
EUROPEAN JOURNAL OF CANCER
Volume 164, Issue -, Pages 39-51Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2021.12.030
Keywords
Breast cancer; Serum markers; Thymidine kinase; Palbociclib; Fulvestrant; Prognostic factors
Categories
Funding
- Pfizer
- IBCSG
- IBCSG: Frontier Science
- Swiss Group for Clinical Cancer Research
- Cancer Research Switzerland
- Oncosuisse
- Cancer League Switzerland
- Foundation for Clinical Cancer Research of Eastern Switzerland
- AURORA study: Breast Cancer Research Foundation (BCRF) [BCRF-19-186, ELFF-19-00]
- Foundation Cancer (Luxembourg)
- National Lottery (Belgium)
- Foundation NIF
- Barrie and Dena Webb
- Candriam
- Fondation Futur 21
- Sogerim
- Think Pink Belgium (SMART Fund)
- Fund Friends of BIG
- Fondazione AIRC per la Ricerca sul Cancro [22869]
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This study investigated the prognostic role of serum thymidine kinase activity (sTKa) in patients with metastatic breast cancer treated with Palbociclib + fulvestrant. The results showed that the changes in sTKa levels during treatment were closely associated with patients' progression-free survival, and high pre-treatment sTKa levels and incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance.
Background: Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine kinase activity (sTKa), in patients treated with Palbociclib + fulvestrant. Patients and methods: PYTHIA was a phase II, single-arm, multicentre, trial that enrolled 124 post-menopausal women with endocrine-resistant hormone receptor-positive/HER2-negative metastatic breast cancer. Serum samples were collected pre-treatment (pre-trt; n = 122), at day 15 of cycle 1 (D15; n = 108), during the one week-off palbociclib before initiating cycle 2 (D28; n = 108) and at end of treatment (n = 76). sTKa was determined centrally using Divitum (R), a refined ELISA-based assay with a limit of detection of 20 Divitum Units (Du)/L. The primary study endpoint was progression-free survival, assessed for its association with pre-and on-treatment sTKa. Results: Data from 122 women were analysed. Pre-treatment sTKa was not associated with clinical characteristics and moderately correlated with tissue Ki-67. Palbociclib + fulvestrant markedly suppressed sTKa levels at D15, with 83% of patients recording levels below limit of detection. At D28, sTKa showed a rebound in 60% of patients. At each timepoint, higher sTKa was associated with shorter progression-free survival (each p < 0.001), with the strongest effect at D15. Conclusions: STKa is an independent prognostic biomarker in patients treated with palbociclib. High pre-treatment sTKa and its incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance. This warrants validation in prospective compar-ative trials. (c) 2022 Elsevier Ltd. All rights reserved.
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