(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer 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 assessing darolutamide + ADT in patients with high-risk biochemical recurrence of prostate cancer.
Up to half of patients whose prostate cancer has been treated with radiotherapy or radical prostatectomy as primary therapy will develop biochemical recurrence, defined as a PSA increase without evidence of metastases on conventional imaging (ie. CT/MRI). Compared with conventional imaging, PSMA PET/CT is a more precise imaging method that may detect small prostate cancer lesions in patients with biochemical recurrence and help avoid unnecessary biopsies. Effective treatment is needed for patients with biochemical recurrence at high risk of metastatic progression, and who have lesions identified by PSMA PET/CT, to delay progression.
Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor with low blood-brain barrier penetration and limited potential for drug-drug interactions. In ARAMIS, darolutamide significantly improved metastasis-free survival and reduced risk of death in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).1-2 ARASTEP is evaluating whether darolutamide + ADT improves radiological progression-free survival by PSMA PET/CT versus placebo + ADT in patients with biochemical recurrence following primary therapy and PSMA PET/CT-positive lesions.
ARASTEP is a global, phase 3, double-blind, placebo-controlled study in which ~750 patients from 192 sites will be randomized to receive oral darolutamide 600 mg twice daily or placebo, both with ADT, for 24 months:
Eligible patients have prostate cancer previously treated with primary radiotherapy or radical prostatectomy followed by adjuvant radiotherapy or salvage radiotherapy or radical prostatectomy alone if unfit for adjuvant radiotherapy/salvage radiotherapy, ECOG performance status 0-1, serum testosterone >150 ng/dL, and high-risk biochemical recurrence. High-risk biochemical recurrence is defined as:
- PSA doubling time < 12 months
- PSA ≥ 0.2 ng/mL above the nadir after primary radical prostatectomy followed by adjuvant radiotherapy or salvage radiotherapy or ≥2 ng/mL after primary radiotherapy only, and
- ≥1 PSMA PET/CT-positive lesion with no evidence of metastasis on conventional imaging
Image-guided radiotherapy or surgery of baseline PSMA PET lesions assessed by blinded independent central review is allowed ≤12 weeks from randomization. Stratification factors are PSA doubling time (<6 vs ≥6–<12 months), intent to treat baseline PSMA PET/CT lesions by blinded independent central review with image-guided radiotherapy/surgery (Yes vs No), and distant ± locoregional vs locoregional-only metastases. The primary endpoint is radiological progression-free survival by PSMA PET/CT assessed by blinded independent central review. Secondary endpoints are:
- Metastasis-free survival by blinded independent central review
- Time to CRPC
- Time to first subsequent systemic antineoplastic therapy
- Time to locoregional progression by PSMA PET/CT
- Time to first symptomatic skeletal event
- Overall survival
- PSA <0.2 ng/mL at 12 months
- Time to deterioration in FACT-P score
- Safety
- Time to symptomatic progression.
Enrollment for ARASTEP began in April 2023 and as of April 2024, 46 patients have been randomized. Recruitment is planned for 222 sites in 23 countries, with the US actively recruiting:
Clinical trial information: NCT05794906.
Presented by: Alex Chehrazi-Raffle, MD, Oncologist, 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 (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 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.