(UroToday.com) The 2023 ASCO annual meeting included a prostate cancer session, featuring a trials in progress presentation by Dr. Xin Gao discussing ARAMON, a phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer. Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration. In the phase 3 ARAMIS study (NCT02200614) of patients with nonmetastatic castration-resistant prostate cancer, treatment with darolutamide significantly improved metastasis-free survival and overall survival versus placebo, with a favorable safety profile.1
Additionally, darolutamide has shown safety and efficacy in mHSPC patients in the ARASENS trial.2 The incidences of central nervous system adverse events (e.g. falls, memory impairment, and depression) showed a ≤2% difference between the darolutamide and placebo groups. Fatigue was the only adverse event with an incidence of > 10% for darolutamide (13.2% vs 8.3% for placebo). In a separate neuroimaging study of healthy volunteers, cerebral blood flow was not altered in patients treated with darolutamide but was significantly reduced in brain areas related to cognition in patients treated with enzalutamide. Furthermore, it is postulated that the low blood–brain barrier penetration of darolutamide may result in lower serum testosterone elevations than those seen with enzalutamide, with the potential of leading to fewer associated feminizing adverse events. Presented at ASCO 2023, the objective of ARAMON (NCT05526248) is to compare the effect of darolutamide and enzalutamide monotherapy on post-treatment testosterone levels in patients with hormone-naive prostate cancer experiencing biochemical recurrence after definitive treatment for localized disease.
ARAMON is a two-stage, open-label, phase 2 study of patients with histologically or cytologically confirmed prostate adenocarcinoma who have biochemical recurrence after radical primary prostatectomy or radiation therapy, with a PSA doubling time of ≤20 months, baseline serum testosterone > 150 ng/dL, and Eastern Cooperative Oncology Group performance status 0 or 1. During a 52-week lead-in phase, 25 patients will receive darolutamide 600 mg twice daily. If criteria based on serum testosterone increase from baseline to week 12 are met, the study will proceed to a 52-week randomized phase in which the effects of darolutamide (600 mg twice daily, n = 20) will be compared with the effects of enzalutamide (160 mg once daily, n = 20). The trial design schema for ARAMON is as follows:
The primary endpoint of both phases is the change in serum testosterone level from baseline to week 12. Secondary endpoints of the randomized phase include:
- The change in serum testosterone levels from baseline to weeks 24 and 52
- PSA at weeks 4, 12, 24, 36, and 52
- Changes in blood levels of markers for glucose, lipid metabolism, and endocrine function related to sex hormones
- Safety assessed through adverse event monitoring
- Quality of life
Exploratory analyses will include bone metabolism and physical function. A summary of the outcomes based on the lead-in and randomized phase are as follows:
Dr. Gao concluded this presentation discussing ARAMON, a phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer by highlighting the following:
- As of May 2023, 7 of the 25 planned patients in the lead-in phase have been enrolled
- The study sites include: Genesis Research LLC, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and Memorial Sloan Kettering Cancer Center
- ARAMON is actively recruiting patients
Presented by: Xin Gao, MD, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142.