ASCO 2022: A Phase III Double Blinded Study of Early Intervention After Radical Prostatectomy with ADT with Darolutamide Versus Placebo in Men at Highest Risk of Prostate Cancer Metastasis by Genomic Stratification (ERADICATE)

(UroToday.com) The 2022 ASCO annual meeting featured a session on prostate cancer, including a trial in progress presentation by Dr. Alicia Morgans discussing ERADICATE, a phase III double blinded study of early intervention after radical prostatectomy with ADT with darolutamide versus placebo in men at highest risk of prostate cancer metastasis by genomic stratification.  Patients with high-risk scores by Decipher molecular testing after prostatectomy have a 5-year metastasis rate of 28% (Decipher 0.6-0.7) and 38% (Decipher > 0.7), likely due to micrometastatic disease. Furthermore, approximately 40% of patients with unfavorable intermediate risk and 80% of high-risk localized prostate cancer have high risk Decipher scores. Clinical trials with intensified systemic treatment are warranted to increase cure rates and address this unmet need. Previous studies of adjuvant ADT in clinically identified high-risk disease have not demonstrated substantial benefit other than in men with lymph node positive disease. Darolutamide is a novel androgen receptor antagonist with demonstrated efficacy in improving metastasis-free survival (MFS) and overall survival (OS) in patients with non-metastatic castration-resistant prostate cancer,1 and OS in patients with metastatic hormone-sensitive prostate cancer (mHSPC).2 Whether treatment with ADT and darolutamide can increase MFS versus ADT plus placebo in the adjuvant setting for men with molecularly identified high-risk prostate cancer is unknown.


Patients with CAPRA-S scores ≥3 and a PSA < 0.2 after radical prostatectomy undergo Decipher testing provided by the trial. Eligible patients with high-risk Decipher scores (> 0.6) will be randomized to treatment with ADT with darolutamide or placebo for 12 months. Patients are stratified by intent to deliver adjuvant radiation and by baseline PSA (undetectable vs detectable but < 0.2 ng/mL). The trial schema for ERADICATE is as follows:

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The primary endpoint is MFS defined by novel PET or conventional imaging. With a sample size of 810 patients, the trial has 80% power with one-sided alpha of 0.025 to detect a HR of 0.60 for the experimental arm vs control arm for the primary endpoint. Secondary endpoints include recurrence-free survival, event-free survival, and quality of life (FACT-P, FACT-Cog, and FACIT-Fatigue), overall survival, and other disease-related outcomes. This trial was activated on December 9, 2020, and is currently enrolling patients.

Clinical trial information: NCT04484818.

Presented by: Alicia K. Morgans, MD, MPH, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022. 

References:

  1. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
  2. 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.
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