Impact of age, number of cycles of chemotherapy and presence of visceral metastases on PSA response in patients on triplet therapy (ADT + darolutamide + docetaxel) for mHSPC: UK real world data from the RECOMMEND study.

67 Background: Darolutamide has authorisation for treatment of metastatic hormone sensitive prostate cancer (mHSPC) in combination with docetaxel chemotherapy and androgen deprivation therapy (ADT), known as triplet therapy, based on ARASENS trial results. The RECOMMEND Study is a prospective real-world evaluation of clinical outcomes in patients with mHSPC treated with this regimen in the UK. Methods: 315 patients were enrolled from 21 UK centres over 20 months from November 2022. Data cut-off was 22 September 2025. Disease characteristics were evaluated. Descriptive statistics have been used for patient demographics and PSA changes with treatment were analysed. Results: Median patient age was 67 (range 38-84) years. Performance status was 0 (62.7%) or 1 (37.3%). 70.2% had a Gleason score ≥8. 78 patients (24.6%) had next generation imaging (NGI) at diagnosis. Most patients were de novo metastatic (92.1%) with metastases (mets) in bone (87.6%), nodes (62.5%), lung (13%) and liver (2.9%). Median time from start of ADT to start of darolutamide was 8 weeks (IQR 4.9-10.6), within the 12 weeks specified by NICE guidelines. At data cut off, 252 patients had reached 12 months (m) from darolutamide start (12mFU) with 26 stopping treatment. Median PSA (ng/mL) at diagnosis was 136 (range 1-6670). At the end of docetaxel median PSA was 0.4 (<0.1–162) which decreased further at 6m FU to 0.18 (0-523). PSA response at 6m FU was PSA 50 93.8% (273/291) and PSA 90 71.8% (209/291) and at 12m FU it was PSA 50 91.9% (226/246) and PSA 90 78.5% (193/246). There was no significant difference in the proportion of patients achieving PSA ≤0.2 ng/mL at 6m or 12m FU with age (<75 vs ≥75), in patients who received ≤4 vs >4 cycles of docetaxel or in those with or without visceral mets (lung/liver) see table. Conclusions: In the RECOMMEND Study, PSA response rates at 6m and 12m after starting darolutamide were similar irrespective of age (<75 vs ≥75), number of cycles of docetaxel (≤4 vs >4) or the presence or absence of visceral mets (lung/liver). This provides important and meaningful real-world evidence in this setting, enabling patients and clinical teams to make informed choices. ADT+darolutamide+docetaxel in mHSPC in the RECOMMEND study shows similar and sustained efficacy as reported in the ARASENS trial. Diagnosis Docetaxel Start 6m FU 12m FU Number 315 312 298 252 Median PSA ng/mL (range) 136 (1-6670) 6.2 (0-2883) 0.18 (0-523) 0.07 (0-86) % PSA ≤0.2 0 3.5 55 64.3 Visceral mets PSA ≤0.2 %(number) No Yes 0 (0/266) 0 (0/49) 3 (8/263) 6.1 (3/49) 55.4 (139/251) 53.2 (25/47) 65 (139/214) 60.5 (23/38) Docetaxel cycles PSA ≤0.2 %(number) ≤4 >4 0 (0/37) 0 (0/277) 2.7 (1/37) 3.6 (10/275) 55.2 (16/29) 55 (148/269) 61.5 (16/26) 64.6 (146/226) Age PSA ≤0.2 %(number) <75 ≥75 0 (0/269) 0 (0/46) 4.1 (11/266) 0 (0/46) 55.3 (141/187) 53.5 (23/43) 63.1 (135/214) 71.1 (27/38)