Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant
- Creators
- Malorni L.
- Tyekucheva S.
- Hilbers F. S.
- Ignatiadis M.
- Neven P.
- Colleoni M.
- Henry S.
- Ballestrero A.
- Bonetti A.
- Jerusalem G.
- Papadimitriou K.
- Bernardo A.
- Seles E.
- Duhoux F. P.
- MacPherson I. R.
- Thomson A.
- Davies D. M.
- Bergqvist M.
- Migliaccio I.
- Gebhart G.
- Zoppoli G.
- Bliss J. M.
- Benelli M.
- McCartney A.
- Kammler R.
- De Swert H.
- Ruepp B.
- Fumagalli D.
- Maibach R.
- Cameron D.
- Loi S.
- Piccart M.
- Regan M. M.
- Others:
- Malorni, L.
- Tyekucheva, S.
- Hilbers, F. S.
- Ignatiadis, M.
- Neven, P.
- Colleoni, M.
- Henry, S.
- Ballestrero, A.
- Bonetti, A.
- Jerusalem, G.
- Papadimitriou, K.
- Bernardo, A.
- Seles, E.
- Duhoux, F. P.
- Macpherson, I. R.
- Thomson, A.
- Davies, D. M.
- Bergqvist, M.
- Migliaccio, I.
- Gebhart, G.
- Zoppoli, G.
- Bliss, J. M.
- Benelli, M.
- Mccartney, A.
- Kammler, R.
- De Swert, H.
- Ruepp, B.
- Fumagalli, D.
- Maibach, R.
- Cameron, D.
- Loi, S.
- Piccart, M.
- Regan, M. M.
Description
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.
Additional details
- URL
- http://hdl.handle.net/11567/1071478
- URN
- urn:oai:iris.unige.it:11567/1071478
- Origin repository
- UNIGE