Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant
- Author(s)
- Malorni, L; Tyekucheva, S; Hilbers, FS; Ignatiadis, M; Neven, P; Colleoni, M; Henry, S; Ballestrero, A; Bonetti, A; Jerusalem, G; Papadimitriou, K; Bernardo, A; Seles, E; Duhoux, FP; MacPherson, IR; Thomson, A; Davies, DM; Bergqvist, M; Migliaccio, I; Gebhart, G; Zoppoli, G; Bliss, JM; Benelli, M; McCartney, A; Kammler, R; De Swert, H; Ruepp, B; Fumagalli, D; Maibach, R; Cameron, D; Loi, S; Piccart, M; Regan, MM; International Breast Cancer Study Group; Breast International Group; PYTHIA Collaborators;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- 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 comparative trials. CLINICALTRIALS. GOV IDENTIFIER: NCT02536742; EudraCT 2014-005387-15.
- Keywords
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Breast Neoplasms/drug therapy/pathology; Cyclin-Dependent Kinase 4; Female; Fulvestrant/therapeutic use; Humans; Male; Piperazines; Prospective Studies; Pyridines; *Thymidine Kinase/therapeutic use; Breast cancer; Fulvestrant; Palbociclib; Prognostic factors; Serum markers; Thymidine kinase
- Department(s)
- Medical Oncology; Laboratory Research
- PubMed ID
- 35172272
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2021.12.030
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-31 03:38:51
Last Modified: 2025-01-31 03:40:50