Results from the pre-planned biomarker analysis performed on the 122 patients enrolled in the PYTHIA trial will be presented on December 9 at SABCS 2020 by Dr Luca Malorni, Principal Investigator of the study and Medical Oncologist at the Prato Hospital, Italy.
The prospective analysis revealed that serum thymidine kinase activity (TKa) may be an independent prognostic biomarker in patients with luminal metastatic breast cancer treated with palbociclib and fulvestrant, helping doctors to identify those patients who will develop primary resistance to the treatment. TKa was measured with the DiviTum essay prognostic tool, recently developed by Swedish biotech Biovica.
TKa was measured at start of treatment and after two weeks. At both timepoints, higher TKa was significantly associated with a shorter progression-free survival (PFS). Along these lines, patients with TKa suppression at two weeks showed a considerable improvement in PFS after six months from treatment initiation, i.e. 85 percent versus 17 percent in patients without strong TKa suppression.
Dr Malorni concluded that a high baseline TKa level and incomplete suppression of TKa during treatment could identify patients with poor prognosis and/or primary resistance to palbociclib and fulvestrant-based treatments.
The combination of CDK4/6 inhibitor palbociclib and fulvestrant is approved for the treatment of patients with luminal metastatic breast cancer whose disease has progressed after prior endocrine therapy. However, a significant proportion of these patients develop treatment resistance within 3 to 6 months of initiation. To date, there are no validated biomarkers to identify such patients. While further investigation is warranted, these preliminary results from patients enrolled in the PYTHIA trial are encouraging, as they show that TKa may represent a novel biomarker to select patients who are candidates for alternative treatment modalities.
PYTHIA (IBCSG 53-14/BIG 14-04; NCT02536742) is a phase II downstream trial of the European AURORA research programme (BIG 14-01; NCT02102165), which aims to identify molecular aberrations in patients with metastatic breast cancer. The purpose of PYTHIA is to find potential biomarkers that can predict patients’ response to the combination of palbociclib with standard endocrine therapy based on fulvestrant.
The study has recruited 122 postmenopausal women with an endocrine-resistant estrogen receptor positive (ER+) and HER2 negative (HER2-) (luminal) metastatic or locally relapsed breast cancer, whose disease has progressed after prior endocrine therapy (1st or 2nd line).
PYTHIA is being conducted in 19 hospitals in Belgium, Italy and the UK. It is sponsored by the International Breast Cancer Study Group (IBCSG) and run in collaboration with the Breast International Group (BIG), with the financial support of Pfizer. Biovica provided the DiviTum diagnostic tool and financial support for the assays and their analysis in PYTHIA.