Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant.
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Date
2022-03-01ICR Author
Author
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 and PYTHIA Collaborators,
Type
Journal Article
Metadata
Show full item recordAbstract
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®, 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.
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Research team
Clinical Trials & Statistics Unit
Language
eng
Date accepted
2022-01-11
License start date
2022-01-11
Citation
European Journal of Cancer
Publisher
ELSEVIER SCI LTD