Efficacy outcomes 12 months after initiation of darolutamide in non-metastatic castrate resistant prostate cancer (nmCRPC) from the real world UK multi-centre RECORD study.

Abstract

83 Background: Darolutamide has authorisation for treatment of non-metastatic Castrate Resistant Prostate Cancer (nmCRPC) based on the ARAMIS trial. The RECORD Study is a prospective real-world evaluation (RWE) of clinical outcomes in patients with nmCRPC treated with darolutamide in the UK. The study will improve understanding of treatment response and duration as well as inform regarding the use of next generation imaging (NGI) and effects of concomitant medication. Methods: Patients were enrolled from 19 centres over a 3-year period from November 2020. Data cut-off was 16 September 2024. Disease characteristics of patients and efficacy up to 12 months (m) after initiation of darolutamide are evaluated. Descriptive statistics will be used for patient demographics. Results: 257 patients were analysed with a median age of 77 (range 52-94) years (y). 52% have a Gleason score ≥8. 30 patients (11.7%) had NGI prior to initiation of darolutamide and 41 (15.8%) were on anticoagulant/antiplatelet medication. ECOG 0:35%, 1:59% and 2:6.2%. Median pre-treatment PSA was 9.7ng/mL and pre-treatment PSA doubling time (PSAdT) was 5 months. The greatest reduction in median PSA values was seen within the first 3m on darolutamide but was still decreasing slightly at 12m. PSA response was as follows: PSA 50 reduction at 3, 6, 9 and 12 months was 74%, 77%, 75% and 73% respectively and PSA 90 reduction at 3, 6, 9 and 12 months was 28%, 38%, 43% and 42% respectively. No differential effect on PSA reduction was seen with Gleason score (<8, ≥8), PSAdT≤6m or >6m, previous treatment (RT or prostatectomy), anticoagulant/antiplatelet medication or those who had NGI. Median duration of treatment on darolutamide did not significantly differ (p=0.067) in patients with PSAdT>6m (104 patients) compared to those with PSAdT≤6m (135 patients). 46 patients (17.9%) have come off treatment within 12m of initiation: 26 (10.1%) disease progression, 8 (3.1%) toxicity (most frequent being fatigue and diarrhoea), 12 other unrelated causes including 1 death. Conclusions: This RWE shows that patients with nmCRPC in clinical practice have comparable outcomes to the ARAMIS trial. Response rates, tolerability and discontinuation rates are similar and in particular only 3.1% discontinuing treatment due to toxicity. Gleason score >8; PSAdT and the use of NGI had no differential impact on PSA response. This is valuable RWE enabling optimisation of treatment in nmCRPC.