ANGLE plc announced the publication of a study using the Parsortix system to identify markers present in CTCs harvested from metastatic mutant-p53 platinum-resistant ovarian cancer (PROC) patients. The study was conducted as an offshoot of the European multi-centre GANNET53 Phase II clinical trial(NCT02012192) funded by the EU 7th Framework Programme (Grant agreement ID: 602602). The study investigated the efficacy of ganetespib in combination with paclitaxel vs.

paclitaxel alone. Patients were enrolled across 12 clinical centres in Germany, Belgium, France, and Austria.   The translational study, which the research team believes is the largest study of CTCs in ovarian cancer (in terms of number of patient samples analysed), was conducted by researchers at the Medical University of Vienna, Austria.

The study analysed a total of 474 blood samples collected from 123 PROC patients at baseline (i.e. prior to first administration of study drugs), and at multiple timepoints over a period of two and a half years during treatment until disease progression. A panel of 27 gene transcripts (RNA) was analysed on Parsortix-harvested CTCs using standard laboratory qPCR analysis.   The authors identified two CTC-associated markers with potential prognostic value.

ERCC1, a key gene of the DNA damage response pathway, was associated with an increased risk of disease progression and worse outcomes, whereas the presence of ESR1, a gene encoding oestrogen receptor alpha (ERa), was associated with a reduced progression risk. The presence of ESR1 transcripts together with concurrent absence of ERCC1 transcripts in CTC-enriched samples at baseline and during treatment cycles was found to be predictive of improved progression free survival (PFS). Whereas the presence of ERCCI transcripts and the absence of ESR1 transcripts at baseline and during treatment cycles indicated a 12.77× greater likelihood (odds ratio) of cancer progression.

  The analysis of these biomarkers has the potential to provide an early indication of PFS ahead of clinical trial results and suggests that CTC characterisation may be a valuable tool for pharma drug trials in the future.   In addition, the authors conclude that molecular characterisation of CTCs before and during treatment has the potential to be a useful tool to monitor ovarian cancer patients and may provide further insights into the biology of this difficult to treat disease. According to clinicaltrials.gov there are 1,024 active interventional studies enrolling more than 825,000 participants in ovarian cancer.