Abstract
10503 Background: CTC are promising biomarkers in mCRPC but have not been prospectively validated for docetaxel treatment (Rx). Using CellSearch technology (J&J), we enumerated CTC in this Phase 3 trial & assessed prognostic value for OS. The aim of this correlative study nested within 0421 was to compare CTC via CellSearch technology to newer microfilter technologies (Cote & Goldkorn PIs RO1 CA141077). Comparative data analysis is ongoing. Methods: CTC were drawn at baseline (d1) & pre-cycle 2 (d21) of Rx & shipped overnight to a central site for enumeration (CTC/7.5 ml). Cox regression evaluated the association between OS and (i) baseline CTC counts & (ii) CTC dynamics (d1 to d21) in pts with good (<5) vs. poor (>=5) baseline CTC counts. Receiver operator characteristic (ROC) analysis and Characteristics & Regression Trees (CART) were used to explore further prognostic CTC cutpoints for 2-yr survival. Results: Of 263 patients (pts) consented, 238 were evaluable at d1 & 232 at d21. At d1 median CTC was 5 (range 0-5916) & d1 CTC < vs. >= 5 was associated with baseline PSA (mean 99 vs. 320 ng/ml, p=0.004) and worse bone pain (36% vs. 51%, p=0.03). There was a significant difference in OS for d1 CTC < vs. >=5, with a hazard ratio (HR) of 2.92 (95% CI 1.92-4.43, p<0.001) after adjustment for PSA & other factors. In pts with low d1 CTC (< 5), an increase in CTC was associated with shorter OS, HR 4.04 (95%CI 1.56-10.44, p=0.004); in pts with high d1 CTC (>=5), a >=2-fold decrease in CTC was associated with longer OS, HR 0.45 (95%CI 0.24-0.84, p=0.012); adjusting for risk factors. D1 CTC and 2-year survival had ROC AUC of 0.781. CART analysis identified prognostic subgroups based on CTC of 0, 1-5, 6-53, and >53: (HR 0.36, 0.77,1.3 and 2.8). Conclusions: In this phase 3 trial, d1 CTC was prognostic of OS after risk factor adjustment. CTC dynamics from d1 to d21 were also prognostic of OS. These data are an exploratory subset analysis of the overall study. Yet, they comprise the largest docetaxel-based prospective cohort to date, which validates a 5 CTC prognostic threshold for OS & identifies new potential prognostic subgroups that may extend the clinical utility of CTC enumeration in mCRPC.