167 Background: Darolutamide (DARO), an androgen receptor inhibitor (ARI), demonstrates low blood–brain barrier penetration, limited drug–drug interactions, robust efficacy across multiple disease settings, and a favorable safety profile, as reported in the phase 3 ARANOTE (NCT04736199), ARAMIS (NCT02200614), and ARASENS (NCT02799602) trials. The open-label, phase 2 ARAMON trial (NCT05526248) investigated the use of DARO monotherapy in patients (pts) with oligometastatic castration-sensitive prostate cancer (CSPC) after biochemical recurrence (BCR). Here, we report the final lead-in outcomes at 52 weeks. Methods: Eligible pts had confirmed CSPC, prior radical prostatectomy (RP) or radiotherapy (RT), prostate-specific antigen (PSA) ≥0.2 ng/mL after RP or ≥2 ng/mL after RT only, with a PSA doubling time ≤20 months, 150 ng/dL, and an ECOG performance status score (PS) 0–1. Prior androgen deprivation therapy of ≤6 months was allowed if >6 months before start of study treatment. Pts received DARO 600 mg twice daily for 52 weeks. The primary endpoint was change in serum testosterone from baseline to week 12 (secondary endpoint: change from baseline to weeks 24 and 52); secondary endpoints were PSA response and safety. Exploratory endpoints included assessment of fat, glucose metabolism, bone turnover, changes in other sex hormones, and quality of life (QoL). Results: Of 23 eligible pts (evaluable set), the median age was 74 years (range 54–84), 61% were white, 91% had ECOG PS 0, and 87% had Gleason score <8. At study entry, median PSA was 6.0 ng/mL (range 2.1–27.4). From the start of DARO treatment, testosterone increased by 53% at week 12, 56% at week 24, and 48% at week 52. Mean serum testosterone concentrations increased through week 4 and then remained stable through week 52. At week 52, deep PSA responses (PSA <0.2 ng/mL) were observed in 70% of pts, and 87% reached a 90% reduction in PSA. DARO had a favorable safety profile with expected side effects for ARI monotherapy. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2, including feminizing TEAEs (gynecomastia, breast pain, hot flush, nipple pain, breast tenderness), which occurred mostly during the first 6 months of DARO. Minimal changes from baseline were observed over 52 weeks in measures of fat, glucose metabolism, bone turnover, and sex hormones (ie, luteinizing hormone, follicle-stimulating hormone, estradiol). QoL (per FACT-P total score) was maintained during the 52-week study. Conclusions: In pts with CSPC after BCR, DARO monotherapy moderately increased testosterone concentrations from baseline to week 12, which remained stable through week 52. Deep PSA responses were observed, and the safety profile of DARO was consistent with known TEAEs of ARI monotherapy. Clinical trial information: NCT05526248 .
Laccetti et al. (2026) studied this question.