ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer

• Published in: European urology 2023-06, Vol.83 (6), p.508-518
• Main Authors: Devos, Gaëtan, Tosco, Lorenzo, Baldewijns, Marcella, Gevaert, Thomas, Goffin, Karolien, Petit, Valentin, Mai, Cindy, Laenen, Annouschka, Raskin, Yannic, Van Haute, Carl, Goeman, Lieven, De Meerleer, Gert, Berghen, Charlien, Devlies, Wout, Claessens, Frank, Van Poppel, Hendrik, Everaerts, Wouter, Joniau, Steven
• Format: Article
• Language: English
• Subjects: Apalutamide; Gallium Radioisotopes; High-risk prostate cancer; Humans; Male; Minimal residual disease; Neoadjuvant; Neoadjuvant Therapy - methods; Prostate - pathology; Prostate-specific membrane antigen positron emission tomography/computed tomography; Prostatectomy - methods; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - surgery; PTEN loss; Residual cancer burden
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2022.09.009

In high-risk prostate cancer patients, neoadjuvant degarelix plus apalutamide prior to radical prostatectomy results in a significantly improved pathological response compared with degarelix alone. However, it is yet unclear whether this superior pathological response will result in an improved oncological outcome. High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). To determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. ARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. Patients were randomly assigned at a 1:1 ratio to degarelix (240–80–80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. The primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. Patients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5–11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p