Prospective assessment of AR splice variant and multi-biomarker expression on circulating tumor cells of mCRPC patients undergoing androgen receptor targeted agents: interim analysis of PRIMERA trial (NCT04188275)

• Published in: Medical oncology (Northwood, London, England) London, England), 2022-06, Vol.39 (8), p.119-119, Article 119
• Main Authors: Francolini, Giulio, Loi, Mauro, Ciccone, Lucia Pia, Detti, Beatrice, Di Cataldo, Vanessa, Pinzani, Pamela, Salvianti, Francesca, Salvatore, Giulia, Sottili, Mariangela, Santini, Costanza, Frosini, Giulio, Visani, Luca, Burchini, Luca, Mattioli, Chiara, Allegra, Andrea Gaetano, Valzano, Marianna, Cerbai, Cecilia, Aquilano, Michele, Salvestrini, Viola, Desideri, Isacco, Mangoni, Monica, Meattini, Icro, Livi, Lorenzo
• Format: Article
• Language: English
• Subjects: Androgens; Antineoplastic Agents - therapeutic use; Biomarkers; Biomarkers, Tumor - genetics; Cancer therapies; Chemotherapy; Clinical outcomes; Hematology; Humans; Internal Medicine; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; Neoplastic Cells, Circulating - pathology; Oncology; Original Paper; Pathology; Prospective Studies; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - genetics; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Treatment Outcome
• ISSN: 1559-131X; 1357-0560; 1559-131X
• DOI: 10.1007/s12032-022-01756-2

Circulating tumor cells detection and ARV7 expression are associated with worse clinical outcomes in metastatic Castration-Resistant Prostate Cancer (mCRPC) undergoing Androgen Receptor Targeted Agents. ARFL, PSMA and PSA may help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCPRC undergoing I line ARTA therapy terminated the planned enrollment in 2020. Here, we present a pre-planned interim analysis with 18 months of median follow-up. RT-qPCR was used to determine the CTC expression of PSA, PSMA, AR and ARV7 before starting ARTA. PSA-drop, Progression-Free and Overall Survival (PFS and OS) and their correlation with CTC detection were reported. Forty-four patients were included. CTC were detected in 43.2% of patients, of whom 8.94% expressed PSA, 15.78% showed ARV7, 63.15% and 73.68% displayed ARFL and PSMA, respectively. Biochemical response was significantly improved in CTC + vs CTC− patients, with median PSA-drop of 18.5 vs 2.5 ng/ml ( p  = 0.03). After a median follow-up of 18 months, 50% of patients progressed. PFS was significantly longer in CTC- patients (NR vs 16 months). Eight (18.2%) patients died, a non-significant trend in terms of OS was detected in favor of CTC− patients (NR vs 29 months, p  = 0.05). AR, PSA and PSMA expression in CTC + had no significant impact on PSA-drop, PFS or OS. PRIMERA-trial confirmed the CTC detection predictive importance in mCRPC patients.