(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium included a prostate cancer session featuring trials in progress and a presentation by Dr. Alex Chehrazi-Raffle discussing the trial design of ARASTEP, a phase 3, randomized, double-blind, placebo-controlled study of darolutamide + ADT in patients with high-risk biochemical recurrence of prostate cancer. Patients with prostate cancer treated with radiotherapy or radical prostatectomy as primary therapy may develop biochemical recurrence, defined as a PSA increase without evidence of metastases on conventional imaging. In fact, up to 50% of patients treated with radiotherapy and 20-30% treated with radical prostatectomy may develop biochemical recurrence without evidence of metastasis.
PSMA PET/CT, a more effective and precise imaging method than conventional imaging, may detect small lesions in patients with biochemical recurrence. Patients with biochemical recurrence at high risk of metastatic progression and who have lesions identified by PSMA PET/CT need effective treatment to delay this progression. Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor, which significantly improved metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).1,2 The ARASTEP study is designed to evaluate whether darolutamide + ADT improves radiographic progression-free survival by PSMA PET/CT vs placebo + ADT in patients with biochemical recurrence following primary therapy and PSMA PET/CT-positive lesions.
Eligible patients for ARASTEP must have prostate cancer treated by primary radiotherapy or radical prostatectomy followed by adjuvant radiotherapy or salvage radiotherapy, or radical prostatectomy alone if adjuvant radiotherapy/salvage radiotherapy was not appropriate, with high-risk biochemical recurrence (defined as 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 lesion of prostate cancer without visible lesions on conventional imaging, and serum testosterone >150 ng/dL.
Approximately 750 patients from 184 sites worldwide will be randomized to oral darolutamide 600 mg twice daily or placebo, both with ADT, for 24 months unless, during this period, there is disease progression, unacceptable toxicity, or any other withdrawal criteria are met. Of note, patients will suspend treatment after 24 months if PSA values are undetectable (< 0.2 ng/mL). Patients whose PSA values are still detectable (≥ 0.2 ng/mL) will continue with the study treatment until PSMA PET/CT progression. The trial design for ARASTEP is as follows:
Image-guided radiotherapy or surgery is allowed within 12 weeks from randomization. Randomization is stratified by PSA doubling time <6 vs ≥6 – <12 months, intent to treat baseline PSMA PET/CT lesions with image-guided radiotherapy/surgery (yes vs no), and distant ± locoregional vs locoregional-only metastases. The primary endpoint is radiographic progression-free survival by PSMA PET/CT, assessed by blinded independent central review. Secondary endpoints include:
- Metastasis-free survival by blinded independent central review
- Time to CRPC
- Overall survival
- Quality of life
- Safety
The study periods include: screening baseline, treatment (24 months), active follow-up, and long-term follow-up:
ARASTEP is planned to recruit patients from 192 sites in 22 countries:
As of December 2023, 13 patients have been randomized.
Clinical trial information: NCT05794906.
Presented by: Alex Chehrazi-Raffle, MD, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md 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.