Sequential monitoring and characterization of circulating tumor cells (CTCs) using the epic sciences platform in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with recently approved therapeutics.

Abstract

78 Background: The enumeration and molecular characterization of circulating tumor cells (CTCs) may allow sequential evaluation of drug-induced changes and mechanisms of drug resistance that cannot be practically performed by tissue biopsies. Methods: We utilized the Epic Sciences platform to identify and characterize traditional CTCs (CK-CD45+) and other CTC subpopulations (CK-CD45- CTCs and small CTCs) in sequential samples obtained from metastatic castration-resistant prostate cancer (mCRPC) patients (pts) receiving abiraterone acetate (AA), enzalutamide (E), or cabazitaxel (C). Peripheral blood was collected pre-treatment, during treatment (at 1 to 4 weeks, to evaluate pharmacodynamics effects) and at progression. Nucleated cells were plated onto glass slides and subjected to immunofluorescence staining for CK, CD45, and AR, and CTC identification by fluorescent scanners. CTCs from a subset of patients were tested for PTEN loss and ERG rearrangements by FISH. CTCs from a second blood sample collected at the same time were captured and enumerated using CellSearch (Veridex). Fresh CRPC biopsies were available for 9 pts. Results: Initial results are available from 24 mCRPC pts (16 pts treated with AA; four with E; four with C; 17 out of 24 previously treated with docetaxel). Pre-treatment, the median CK+CD45- CTC count was 3.5 (range 0 to 98) cells/mL blood. Eleven pts had more than or equal to 5 CK+CD45- CTCs/mL pre-treatment and 5 out of 11 pts had an Epic CTC conversion to less than 5 CK+CD45- CTCs/mL with treatment. 8 out of 11 pts had a decline in CK+CD45- CTC count greater than 30%. Changes in AR expression and AR subcellular localization were observed during treatment as well as changes in count of CTC subpopulations. CellSearch count was available for 22 out of 24 pts. Twelve out of 22 had more than or equal to five CTCs/7.5mls captured using CellSearch, including 7 out of 12 with more than or equal to five CTCs/ml using Epic platform. Conclusions: Enumeration and molecular characterization of CTCs on the Epic Sciences platform during treatment is feasible and demonstrates drug-induced changes associated with changes in CTC count, AR expression and AR subcellular localization. These assays warrant further studies to validate their role as clinically useful biomarkers in mCRPC.