Circulating tumor cells and clinical outcomes in men with metastatic hormone sensitive prostate cancer treated with enzalutamide and docetaxel: Analysis of the ENZADA trial.

e17093 Background: Circulating tumor cell enumeration is a minimally invasive biomarker that has been shown to be prognostic for overall survival (OS) in metastatic castration resistant prostate cancer but has not been evaluated in metastatic hormone sensitive prostate cancer (mHSPC) receiving chemohormonal therapy. Methods: We evaluated the prognostic value of circulating tumor cell (CTC) enumeration (CTC/mL) and AR-V7 status (Epic Sciences) at baseline and post-docetaxel as an exploratory endpoint from the ENZADA trial (NCT03246347), a single arm phase II trial of men with mHSPC treated with androgen deprivation therapy, enzalutamide, and docetaxel. Endpoints included 52-week PSA complete response (CR) (PSA <0.2) rate, OS and time to castration resistance (TTCR). Fisher’s exact tests, Cox proportional hazard models, and log-rank tests were used to associate CTC enumeration with clinical outcomes. Results: Thirty-six enrolled men had a baseline CTC count collected, and 35 had CTCs measured post-docetaxel. CTC count of 2+/mL was found in 10/36 (28%) men at baseline and was not associated with the rate of 52-week PSA CR, OS or TTCR. Similarly, CTC > 0/mL post-docetaxel was detected in 12/35 (34%) men and was not associated with OS or TTCR; however post-docetaxel CTC count > 0/mL was associated with a higher 52-week PSA CR (11/12, 92%) vs CTC count = 0 (12/23, 52%). AR-V7 was only detected in 1/36 (3%) men at baseline. A binary variable of men whose CTC level either increased (9/35) or decreased/remained stable (26/35) from baseline to post-docetaxel was similarly not associated with OS, TTCR, or 52-week PSA CR. However, among those with 52-week PSA CR, rising CTC level from baseline to post-docetaxel was associated with significantly shorter TTCR and a trend towards shorter OS compared to those with 52-week PSA CR and stable or decreased CTC level (Table). Conclusions: Baseline CTC burden or post-docetaxel CTC burden alone was not prognostic in men with mHSPC treated with ADT, enzalutamide, and docetaxel; however, a rising CTC count from baseline to post-docetaxel identified a subset of men who, despite a PSA CR at 52 weeks, had worse OS and TTCR in this cohort. As anticipated, participants who did not achieve a 52-week PSA CR had worse outcomes. Whether an increase in CTC level from baseline to the time after docetaxel adds prognostic value beyond depth of PSA response in mHSPC warrants further study. Clinical trial information: NCT03246347 . TTCR Hazard Ratio (95% CI) OS Hazard Ratio (95% CI) 52-Week PSA 52-Week PSA CR No CR CR No CR CTC change from baseline Decrease/stable Reference HR 18.6 (2.4 to 147.5) CTC change from baseline Decrease/stable Reference HR 11.6 (1.5 to 94.4) Increased HR 10.7 (1.2 to 96.9) Increased HR 6.7 (0.7 to 64.7) Log-rank p=0.001 Log-rank p=0.018