ASCO 2022: Open-Label Study of Androgen Receptor Inhibition With Darolutamide + ADT Versus ADT in Men With mHSPC Using an External Control Arm (ARASEC)

(UroToday.com) The 2022 ASCO annual meeting featured a session on prostate cancer, including a trial in progress presentation by Dr. Neal Shore discussing ARASEC, an open-label study of androgen receptor inhibition with darolutamide + ADT versus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC) using an external control arm. Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor that significantly improved metastasis-free survival by ~2 years and reduced the risk of death by 31% vs placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).¹ In patients with mHSPC, darolutamide + ADT + docetaxel significantly reduced the risk of death by 32.5% versus placebo + ADT + docetaxel (HR 0.68, 95% CI 0.57-0.80) in the phase 3 ARASENS study.² Darolutamide has a favorable safety and tolerability profile, with only ≤2% difference vs placebo for most adverse events of interest (falls, fractures, hypertension, mental impairment). Fatigue was the only adverse event with > 10% incidence in the darolutamide arm (13.2%; placebo, 8.3%). Darolutamide has shown lower blood–brain barrier penetration than other androgen receptor inhibitors in preclinical models (supported by human neuroimaging studies), which may lead to a lower risk of central nervous system-related adverse events and has a low potential for drug–drug interactions. For patients with mHSPC, the combination of darolutamide and ADT is expected to offer a favorable benefit–risk profile. ARASEC will evaluate the efficacy and safety of darolutamide + ADT in mHSPC in the US (NCT05059236) and complement the data in the ongoing ARANOTE study (NCT04736199).

ARASEC is a US-based, phase 2, open-label, single-arm study with an external control arm. Eligible patients will have confirmed adenocarcinoma of the prostate, radiologic evidence of metastatic disease by conventional imaging, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2. Patients with mHSPC will receive darolutamide 600 mg twice daily plus ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). The control arm for ARASEC will be derived from the 393 patients with mHSPC treated with ADT alone in the CHAARTED trial.³ Patients in the active arm will be matched 1:1 to patients in the control arm using important baseline characteristics such as age, ECOG PS, extent of disease defined as low or high volume according to CHAARTED, and presence of bone and visceral metastases. The trial schema for ARASEC is as follows:

ASCO 2022_Shore_ARASEC_0

Study duration was defined as the time from the first patient’s first visit until either the event count threshold triggering the primary endpoint analysis has been met or all patients have been followed for ≥2 years after enrollment, whichever occurs later. The primary endpoint is progression-free survival (PFS), defined in CHAARTED as the time from enrollment to PSA progression, clinical progression (including radiological or symptomatic progression or clinical deterioration), or death, whichever occurs first. Secondary endpoints include:

Overall survival
Radiographic PFS
Time to CRPC
Complete PSA response rate at 6 months
Safety

ARASEC is currently enrolling at 6 sites, with a target enrollment of 200 patients at 30 sites. The first patient was enrolled in November 2021 and the primary completion is anticipated in the 2^nd quarter of 2024. As of May 4, 2022, the following sites are included in the United States:

ASCO 2022_Shore_ARASEC_1

Clinical trial information: NCT05059236.

Presented by: Neal D. Shore, MD, FACS, Carolina Urologic Research Center, Myrtle Beach, SC

Co-Authors: Mark A. Preston, Justin R. Gregg, Simpa Samuel Salami, Ashley Ross, Amanda Bruno, Shankar Srinivasan, Niculae Constantinovici, Jorge A. Ortiz, Frank Verholen, Rana R. McKay

Affiliations: Carolina Urologic Research Center, Myrtle Beach, SC, Brigham and Women's Hospital, Boston, MA, The University of Texas MD Anderson Cancer Center, Houston, TX, University of Michigan, Ann Arbor, MI, Johns Hopkins Medicine, Baltimore, MD, GlaxoSmithKline, Collegeville, PA, Bayer HealthCare, Whippany, NJ, Bayer Consumer Care AG, Basel, Switzerland, Imclone Syst Inc., Miami, FL, Bayer Consumer Care, Basel, Switzerland, University of California San Diego Health, La Jolla, CA

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.

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