Abstract 671P
Background
Advances in treatment of metastatic castration-resistant prostate cancer (mCRPC) led to different treatment options, including androgen receptor targeted agents (ARTA) and taxane-based chemotherapy. Radiopharmaceuticals represent additional treatment options for these patients (pts) and recent data suggest a promising response rate after treatment with Lutethium-PSMA. However, biomarkers to drive the optimal therapeutic sequence are still missing. The presence of the androgen-receptor (AR) splice variants (ARV7 and ARFL) and the membrane-bound glycoprotein prostate-specific membrane antigen (PSMA) expression in mCRPC pts has been recently investigated. Hence, we explored the predictive value of ARV7, ARFL and PSMA combined expression on circulating tumor cells (CTCs) detected in mCRPC pts undergoing I line ARTA therapy (PRIMERA trial).
Methods
Pts with mCRPC eligible for ARTA were prospectively enrolled. Twelve statuses were defined according to the combined expression of biomarkers (ARV7 and ARFL variants and PSMA) detection on CTCs at baseline. Multiple regression was performed to explore the correlation between status and treatment response features (overall PSA drop, 8 weeks PSA drop, PSA determined at 8 weeks, PSA nadir in CRPC status and time to CRPC).
Results
Overall, cohort was composed of 28 pts. CTCs were detected in 15 (53.6 %) pts. PSMA, ARV7 and ARFL were expressed in 11, 2 and 9 pts, respectively. ARFL was significantly associated with increased PSA drop and overall PSA drop (P 0.02 and 0.04, respectively). ARFL-/PSMA+ status was significantly predictive for higher PSA at 8 weeks (P 0.01) and higher PSA nadir in CRPC status (P 0.01). Moreover, ARFL+/PSMA- status was shown to be predictive for reduced time to CRPC development (P 0.02). ARV7-/ARFL+ status was shown to predict an increased PSA drop (P 0.01 and R2 0.2) and overall PSA drop (P 0.02).
Conclusions
The combined expression of ARFL, PSMA and ARV7 may affect biochemical treatment response and may be related to biological aggressiveness of disease. Our data prompt further prospective evidence to confirm biological rationale and implication of these biomarkers on treatment sequencing for mCRPC.
Clinical trial identification
NCT04188275, December 1, 2018.
Editorial acknowledgement
Legal entity responsible for the study
Radiotherapy and Oncology Department, University of Florence.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.