(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Alicia Morgans discussing ARASTEP, a phase 3, randomized, double-blind, placebo-controlled study assessing darolutamide + ADT in patients with high-risk biochemical recurrent prostate cancer. Patients with prostate cancer treated with radiotherapy or radical prostatectomy as primary therapy may develop biochemical recurrence – a PSA increase with no evidence of metastases on conventional imaging (ie. MRI/CT). PSMA PET/CT is more sensitive than conventional imaging and may detect lesions in patients with biochemical recurrence that conventional imaging cannot. Biochemical recurrence is an indicator of disease progression and warrants effective treatment to delay further progression, particularly if lesions are detected by PSMA PET/CT.
The androgen receptor inhibitor darolutamide is structurally different by design to deliver robust clinical efficacy with a differentiated tolerability profile. In the phase 3 ARAMIS trial,1 darolutamide significantly improved metastasis free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). ARASTEP is a phase 3 trial (NCT05794906) evaluating whether darolutamide + ADT improves radiological progression free survival by PSMA PET/CT versus placebo plus ADT in patients with high-risk biochemical recurrence and PSMA PET/CT-positive lesions following primary therapy.
Key eligibility criteria included:
- Prior primary radiotherapy or radical prostatectomy ± adjuvant radiotherapy or salvage radiotherapy
- High-risk biochemical recurrence: PSA doubling time <12 months and PSA ≥0.2 ng/mL after primary radical prostatectomy (± adjuvant radiotherapy/salvage radiotherapy) or PSA ≥2 ng/mL above nadir after primary radiotherapy only
- ≥1 PSMA PET/CT-positive prostate cancer lesion with no visible lesions on conventional imaging
- Serum testosterone ≥150 ng/dL
ARASTEP is planned for 970 patients from 23 countries to be randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, both with ADT, for 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent. During the 24-month treatment period, patients will be monitored for safety every 12 weeks and every 24 weeks for PSMA PET/CT and conventional imaging events. After 24 months, patients with PSA values ≥0.2 ng/mL will continue study treatment as part of active follow-up until PSMA PET/CT progression is confirmed by blinded independent central review (BICR), followed by long-term follow-up for conventional imaging progression. Patient stratification factors are PSA doubling time (<6 versus ≥6–<12 months), intent to treat baseline PSMA PET/CT lesions with image-guided radiotherapy/surgery (yes versus no), and distant ± locoregional vs locoregional-only lesions:
The primary endpoint is radiological progression free survival by PSMA PET/CT assessed by BICR, and secondary endpoints include metastasis free survival on conventional imaging by BICR, time to CRPC, overall survival, quality of life, and safety.
As of April 2025, 616 patients have been randomized from 243 sites in 23 countries:
Presented by: Alicia K. Morgans, MD, MPH, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
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.