(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to a prostate cancer trials in progress poster session. Dr. Andrew Laccetti presented ARAMON, a phase 2, randomized, open-label study comparing darolutamide and enzalutamide monotherapy’s effects on serum testosterone levels in patients with castration-sensitive prostate cancer in the setting of biochemical recurrence.
Darolutamide, a structurally distinct and highly potent androgen receptor pathway inhibitor (ARPI), has low blood-brain barrier penetration and limited potential for drug-drug interactions. In phase 3 clinical trials, darolutamide has shown significant efficacy and a favorable safety profile:
- In the ARAMIS study of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), darolutamide plus androgen-deprivation therapy (ADT) significantly improved metastasis-free survival by nearly two years (HR 0.41, 95% CI 0.34-0.50; P<0.001), reduced the risk of death by 31% (HR 0.69, 95% CI 0.53-0.88; P=0.003), and had a similar low incidence of adverse events compared with placeb1,2
- In the ARASENS study of patients with metastatic hormone-sensitive prostate cancer (mHSPC), the addition of darolutamide to ADT and docetaxel significantly reduced the risk of death by 32.5% (HR 0.68, 95% CI 0.57-0.80; P<0.0001), with a favorable safety and tolerability profile and similar incidences of adverse events observed between treatment groups3,4
In a neuroimaging study of healthy volunteers (NCT03704519), it was demonstrated that treatment with darolutamide did not alter cerebral blood flow, whereas enzalutamide-treated patients had significantly reduced cerebral blood flow in brain areas related to cognition.5 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 to reduce adverse events.
ARAMON is a two-stage, open-label, phase 2 study of patients with histologically or cytologically confirmed prostate adenocarcinoma who experienced BCR following radical prostatectomy or primary radiotherapy and have evidence of <5 asymptomatic oligometastases.
The study consists of 2 phases:
- During the lead-in phase, 25 patients will receive darolutamide 600 mg twice daily for 52 weeks. In the randomized phase, approximately 40 patients will be randomized 1:1 to darolutamide (600 mg twice daily) or enzalutamide (160 mg once daily) for a total duration of 52 weeks
The primary objective of the lead-in phase of ARAMON is to evaluate the impact of darolutamide monotherapy on serum testosterone levels over a 12-week intervention period in patients with castration-sensitive prostate cancer experiencing BCR after definitive treatment for localized disease.
The primary objective of the randomized phase of ARAMON is to compare the effects of treatment with darolutamide versus enzalutamide monotherapy on serum testosterone levels over a 12-week intervention period in a separate population of patients with the same stage of prostate cancer. The remaining study endpoints are summarized below:
As of November 2023, the lead-in phase of ARAMON is fully enrolled and has closed enrollment.
Presented by: Andrew Laccetti, MD, MS, Assistant Attending of Genitourinary Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
References:
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
- Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049.
- 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.
- Hussain M, Tombal B, Saad F, et al. Darolutamide plus androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer by disease volume and risk subgroups in the phase III ARASENS trial. J Clin Oncol. 2023 Jul 10;41(20):3595-3607.
- Williams SCR, Mazibuko N. O’Daly O, et al. Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Target Oncol. 2023;18(3):403-413.