dc.contributor.author | Malorni, L | |
dc.contributor.author | Tyekucheva, S | |
dc.contributor.author | Hilbers, FS | |
dc.contributor.author | Ignatiadis, M | |
dc.contributor.author | Neven, P | |
dc.contributor.author | Colleoni, M | |
dc.contributor.author | Henry, S | |
dc.contributor.author | Ballestrero, A | |
dc.contributor.author | Bonetti, A | |
dc.contributor.author | Jerusalem, G | |
dc.contributor.author | Papadimitriou, K | |
dc.contributor.author | Bernardo, A | |
dc.contributor.author | Seles, E | |
dc.contributor.author | Duhoux, FP | |
dc.contributor.author | MacPherson, IR | |
dc.contributor.author | Thomson, A | |
dc.contributor.author | Davies, DM | |
dc.contributor.author | Bergqvist, M | |
dc.contributor.author | Migliaccio, I | |
dc.contributor.author | Gebhart, G | |
dc.contributor.author | Zoppoli, G | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Benelli, M | |
dc.contributor.author | McCartney, A | |
dc.contributor.author | Kammler, R | |
dc.contributor.author | De Swert, H | |
dc.contributor.author | Ruepp, B | |
dc.contributor.author | Fumagalli, D | |
dc.contributor.author | Maibach, R | |
dc.contributor.author | Cameron, D | |
dc.contributor.author | Loi, S | |
dc.contributor.author | Piccart, M | |
dc.contributor.author | Regan, MM | |
dc.contributor.author | International Breast Cancer Study Group, | |
dc.contributor.author | Breast International Group and PYTHIA Collaborators, | |
dc.date.accessioned | 2022-01-18T15:26:13Z | |
dc.date.available | 2022-01-18T15:26:13Z | |
dc.date.issued | 2022-03-01 | |
dc.identifier.citation | European Journal of Cancer | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4966 | |
dc.description.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®, 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. | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCI LTD | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
dc.title | Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-01-11 | |
rioxxterms.version | AM | |
rioxxterms.licenseref.startdate | 2022-01-11 | |
dc.relation.isPartOf | European Journal of Cancer | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Accepted | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Trials & Statistics Unit | |
dc.contributor.icrauthor | Bliss, Judith | |