MP22-19\u2003NEOADJUVANT APALUTAMIDE (ARN-509) AND RADICAL PROSTATECTOMY IN TREATMENT OF INTERMEDIATE TO HIGH RISK PROSTATE CANCER (NEAR)–INITIAL RESULTS OF A PHASE II TRIAL

Abstract

INTRODUCTION AND OBJECTIVES: The NEAR trial is a phase II single arm study of neoadjuvant apalutamide (ARN-509) and radical prostatectomy (RP) in the treatment of D’Amico intermediate and high-risk prostate cancer (Clinicaltrials.gov identifier: NCT03124433). METHODS: Eligibility criteria included patients between 21-75 years old diagnosed with conventional adenocarcinoma, excluding those with radio-recurrent disease, and poor ECOG status (3 or below). Participants received ARN509 240mg daily for 12 weeks followed by RP. Primary outcomes included tumour response defined by residual cancer burden (RCB) and post-therapy morphologic characterization (groups A-C, with C being the worst response), and post-operative serum PSA levels below 0.03ng/ml. Secondary outcomes included prevalence of significant adverse events (AE) with ARN509 and operative complications following RP. Statistical significance was defined as p<0.05. RESULTS: Of the 30 subjects planned for enrolment, 17 participants have completed the study. The median age was 68 years, and serum PSA at recruitment was 11.0 ng/mL. They comprised D-Amico intermediate-risk n=9 (53%) and high-risk n=8 (47%), with ISUP grade group distributions of 1(n=1, 6%), 2(n=9, 53%), 3(n=6, 35%) and 4-5(n=1, 6%). There were 82% of subjects who achieved post-prostatectomy nadir PSA levels, and post-therapy morphology classifications were group A (45%), group B (10%) and group C (45%). The median RCB index was 1.80 (1.28 to 3.48) (range) and the median reduction in RCB was 19% (range 7% to 40%, p=0.0037). The reduction of serum PSA after neoadjuvant apalutamide alone was 93.4% (range 61.2 to 99.3, p=0.0005). There was one subject with an unrelated grade III AE, and no subjects with Clavien-Dindo grade III and above surgical complications. CONCLUSIONS: Initial results of the phase II NEAR trial show safe and reasonable oncological outcomes in patients with significant organ confined prostate cancer. Additional outcomes following trial completion may help warrant support for future phase III studies. Source of Funding: Clinical trial funding from Janssen