Photo Credit: Md Saiful Islam Khan
The following is a summary of “Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial,” published in the September 2024 issue of Urology by Ruiz-Vico et al.
The PRESIDE trial (NCT02288247) established that extending enzalutamide treatment beyond progression improves progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing docetaxel therapy.
This study evaluates the correlation between PFS and circulating tumor DNA (ctDNA) levels before and after one cycle of docetaxel (Cycle 2 Day 1 [C2D1]), and assesses the predictive value of liquid biopsy resistance biomarkers (LBRB), including plasma androgen receptor (AR) gain and circulating tumor cells (CTCs) expressing AR splice variant 7 (CTC-AR-V7), before continuing enzalutamide or placebo.
Researchers included 157 patients who consented to the biomarker substudy and provided blood samples before initiating docetaxel with enzalutamide or placebo. Plasma DNA was analyzed using a bespoke next-generation sequencing panel (PCF_SELECT), and CTCs were evaluated for AR-V7 expression (Epic Sciences, San Diego, CA, USA). Statistical analyses included Cox proportional hazards models, Kaplan-Meier survival curves, and restricted mean survival time (RMST) at 18 months. Pre-docetaxel ctDNA detection (present in 55% of patients) was significantly associated with reduced PFS compared to undetectable ctDNA (8.1 vs. 10.8 months; hazard ratio [HR] = 1.78, p = 0.004). Similarly, persistent or rising ctDNA levels at C2D1 (35/134 patients) correlated with shorter PFS (5.5 vs. 10.9 months; HR = 1.95, 95% CI = 1.15–3.30, p = 0.019). Patients positive for LBRB (62 patients) did not show a benefit from continuing enzalutamide (HR = 0.78, 95% CI = 0.41–1.48, p = 0.44; RMST: 7.9 vs. 7.1 months, p = 0.50), whereas those negative for resistance biomarkers (87 patients) exhibited significantly prolonged PFS (HR = 0.49, 95% CI = 0.29–0.82, p = 0.006; RMST: 11.5 vs. 8.9 months, p = 0.005). About 8 patients were unevaluable, and an exploratory analysis indicated increased copy-number gains (CDK6/CDK4) at docetaxel progression.
The limitations of this study include relatively low detection rates of CTC-AR-V7. Future research is needed to confirm the impact on overall survival. These findings suggest that liquid biopsy can provide early indicators of docetaxel resistance, guiding patient selection for continued enzalutamide therapy and highlighting cell cycle gene alterations as potential resistance mechanisms in mCRPC.
Source: sciencedirect.com/science/article/pii/S2588931124001883
