Darolutamide monotherapy in patients with castration-sensitive prostate cancer (CSPC) after biochemical recurrence (BCR): ARAMON lead-in phase results.
Authors: Laccetti Andrew Leonard , Smith Matthew R , Scher Howard I. , Nowfar Sepehr , Einstein David Johnson , Martin Benjamin , Adorjan Patrick , Dissanayake Manjari , Verholen Frank , Gao Xin 
Published: February 2025

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Background:
Treatment of a BCR typically starts with androgen-deprivation therapy (ADT), which is limited by treatment-emergent adverse events (TEAEs) that adversely impact patients’ quality of life. The second-generation androgen receptor inhibitors (ARIs), enzalutamide and apalutamide, were explored in patients with BCR, demonstrating a reduction in prostate-specific antigen (PSA) but an increase in testosterone levels from baseline at week 25 of 114% and 134% (1,2). Given the strong efficacy and favorable tolerability of darolutamide, the open-label, phase 2 ARAMON study (NCT05526248) was conducted to investigate the reactive testosterone increase associated with darolutamide monotherapy in patients with CSPC after BCR. Here, we report lead-in phase results.
Methods:
Eligible patients had confirmed CSPC and a prior radical prostatectomy or radiotherapy, with a rising PSA doubling time ≤20 months, <5 asymptomatic metastatic lesions, serum testosterone >150 ng/dL, and ECOG performance status (PS) of 0/1. Patients received darolutamide 600 mg twice daily for 52 weeks. ADT was not allowed. The primary endpoint was the change in testosterone from baseline to week 12 and secondary endpoints of PSA response and TEAEs up to January 17, 2024 are also reported.
Results:
Of 23 evaluable patients, the median age was 74 (range, 54–84) years, the majority were white (n=14), had an ECOG PS of 0 (n=21), and Gleason score <8 (n=20). At study entry, the median PSA was 6.0 (range, 2.1–27.4) ng/mL, and most patients had nonmetastatic CSPC (n=15), 5 patients had oligometastatic disease (bone metastatic lesions <5), and 3 patients had soft tissue metastases (all <2 cm). At week 12, the mean percent increase in testosterone from baseline was 53% (95% CI, 33–76). Deep PSA responses to <0.2 ng/mL were observed in 15 patients at week 12. Feminizing TEAEs (gynecomastia, breast pain, breast tenderness, nipple pain, breast enlargement, breast mass, breast swelling, and hot flush) occurred in 18 patients and were grade 1 or 2 in 17 patients; 4 patients had dose modifications due to feminizing TEAEs and 2 patients received tamoxifen for gynecomastia. At week 12, none of the patients had discontinued darolutamide due to TEAEs. One patient discontinued darolutamide due to gynecomastia after week 12. Fatigue and hypertension occurred in 5 and 4 patients, all of which all events were grade 1/2 in severity.
Conclusions:
In patients with CSPC, darolutamide monotherapy increased baseline testosterone levels to a lesser degree than previously reported for other ARI agents administered as monotherapy and provided deep PSA responses at week 12. Darolutamide was well tolerated, with a low rate and severity of TEAEs. The ARAMON lead-in phase is limited by its single-arm, open-label design, and small sample size. 1. Tombal et al 2014. 2. Maluf et al 2021. Clinical trial information:
NCT05526248
.