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The ARAMIS Trial: Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
Videos
Non-Metastatic Castration-Resistant Prostate Cancer in the Era of PSMA PET Imaging - Aaron Berger
Efficacy and Safety of Darolutamide in the Planned Subgroup Analysis of the Phase 3 ARAMIS Trial, Journal Club - Zachary Klaassen
Progression Patterns by Types of Metastatic Spread, PSA, and Clinical Symptoms - Post-Hoc Analyses of ARAMIS - Alicia Morgans
Time Course Profile of Adverse Events With Darolutamide in the ARAMIS Trial – Christian Gratzke
Delayed Deterioration in Patient Quality of Life, the Impact of Darolutamide on Local Symptoms in the ARAMIS Trial – Neal Shore
Overall Survival Data from the Global, Phase 3 ARAMIS Trial in Men with Non Metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Karim Fizazi
Significantly Longer Metastasis-Free Survival and Overall Survival in the ARAMIS Trial, Nonmetastatic Castration-Resistant Prostate Cancer - Christopher Wallis & Zachary Klaassen
ARAMIS Trial Demonstrates Significant Improvement in Overall Survival in nmCRPC - Neal Shore
Overall Survival Results of Phase III ARAMIS Study of Darolutamide Added to ADT for Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Karim Fizazi
ARAMIS Trial: Darolutamide Demonstrates Improved Overall Survival in Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) - Fred Saad
Prolonging Overall Survival in Men with Non-metastatic Castration Resistant Prostate Cancer ARAMIS Trial - Neal Shore
Darolutamide Treated Patients Maintained Quality of Life in ARAMIS Trial - Fred Saad
ARAMIS Trial in Prostate Cancer: Impact of Darolutamide on Pain and Quality of Life - Karim Fizazi
Darolutamide Demonstrates Efficacy and Safety in Men with nmCRPC - Neeraj Agarwal
ARAMIS - Efficacy and Safety of Darolutamide in nmCRPC - Karim Fizazi
Phase III ARAMIS Trial Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint - Tom Keane

Enhancing Androgen Blockade in Nonmetastatic Castration-Resistant Prostate Cancer

Publications
Articles and Abstracts

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy.

Aim: Darolutamide significantly improved metastasis-free survival (MFS) and overall survival (OS) versus placebo in the phase III ARAMIS study. We evaluated outcomes in Black/African-American patients in ARAMIS.

Context: Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis–targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit.

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo.

In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

This is a summary of a publication about the ARAMIS (Androgen Receptor Antagonizing Agent for Metastasis-free Survival) trial, which was published in the New England Journal of Medicine in September 2020.

Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial.

Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.

Patients with non-metastatic castration-resistant prostate cancer (nmCRPC, formerly known as M0 CRPC) have rising prostate-specific antigen (PSA) levels despite castrate levels of testosterone with approved androgen deprivation therapy (ADT) and no detectable metastases on conventional imaging with computed tomography (CT) and bone scans.1
San Francisco, CA (UroToday.com)  -- Results from the preplanned final overall survival analysis of the Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial that investigated NUBEQA® (darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) show a significant improvement in overall survival (OS) in patients receiving NUBEQA plus androgen deprivation therapy (ADT) compared to placebo plus ADT.

In July 2019, darolutamide became the newest available oral androgen receptor inhibitor approved by the FDA for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. The Phase 3 ARAMIS trial evaluated darolutamide with androgen deprivation therapy (ADT) versus ADT plus placebo for nmCRPC patients and demonstrated significant improvement in metastasis-free survival (MFS), extending MFS to 40 months for those treated with darolutamide as opposed to 18 months for patients randomized to the ADT + placebo arm.

Published Date: September 2019

Androgen deprivation therapy (ADT) is the longstanding initial treatment for advanced hormone-sensitive prostate adenocarcinoma. Nonetheless, patients who are initiated on ADT will invariably progress by developing prostate cancer cellular clonal populations, which creates a phenotype of more castration-resistant disease with more aggressive biology.1

Chicago, IL (UroToday.com)  -- Darolutamide, an androgen receptor inhibitor, has received FDA approval for the treatment of patients with nonmetastatic castration resistant prostate cancer (CRPC)1 This priority review is based on the Phase III ARAMIS trial evaluating darolutamide plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS).
BACKGROUND: Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.
San Francisco, CA USA (UroToday.com) -- The Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial that investigated darolutamide in men with non-metastatic castration-resistant prostate cancer (nmCRPC), met its primary endpoint.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Alicia K. Morgans, MD, MPH
The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a prostate cancer abstracts poster session. Dr. Alicia Morgans presented the results of an ad-hoc analysis from ARAMIS evaluating the health-related quality of life deterioration-free survival by PSA decline in darolutamide-treated patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC).
Presented by Neal D. Shore, MD, FACS
The 2023 AUA annual meeting included an advanced prostate cancer session, featuring a presentation by Dr. Neal Shore discussing data from the ARAMIS rollover study assessing treatment duration and long-term safety and tolerability with darolutamide in nmCRPC.
Presented by Neal D. Shore, MD, FACS
The 2023 GU ASCO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Neal Shore discussing long-term safety and tolerability of darolutamide and duration of treatment in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) from the ARAMIS Rollover Study.
Presented by Alicia K. Morgans, MD, MPH
At the 2022 ASCO Annual Meeting, the poster session focused on Prostate, Testicular, and Penile cancers included a presentation from Dr. Alicia K. Morgans describing progression patterns of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial.
Presented by Karim Fizazi PhD, MD

Dr. Fizazi presented a poster focused on the effects of comorbidities and concomitant medications among patients on the ARAMIS trial which evaluated darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC).

Presented by Christian J. Gratzke, MD
The ESMO 2021 annual meeting’s prostate cancer session included a presentation by Dr. Christian Gratzke discussing the time course profile of adverse events with darolutamide in the ARAMIS phase 3 trial.
Presented by Karim Fizazi, MD, PhD
Darolutamide (DARO) is a structurally distinct androgen receptor inhibitor (ARI) that has been demonstrated to significantly prolong metastasis-free survival and overall survival in the ARAMIS trial.1
Presented by Susan Feyerabend
Darolutamide significantly prolonged metastasis-free survival (MFS) and overall survival (OS) vs placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS.
Presented by Karim Fizazi, MD, PhD
Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) need therapy that prolongs survival with little added toxicity, thus preserving quality of life.
Presented by Neal D. Shore, MD, FAC
In plenary abstract presentation in the Poster Highlights Session: Prostate Cancer - Localized Disease session at the 2021 ASCO GU meeting, Dr. Shore and colleagues presented an analysis examining the effect of crossover on the overall survival benefit seen in ARAMIS.
Presented by Matthew R. Smith, MD, Ph.D
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in nmCRPC
Presented by Karim Fizazi, MD, Ph.D.
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, PhD
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, Ph.D.
Darolutamide is a unique androgen receptor inhibitor, FDA approved in July 2019 for the treatment of non-metastatic castration-resistant prostate cancer. This approval was based on ARAMIS,1 a large multicenter double-blind, placebo-controlled study that randomized 1500 patients to 600 milligrams of darolutamide twice a day or placebo.
Presented by Peter Albers, MD
Barcelona, Spain (UroToday.com) In the last year, we have had three new treatment options emerge for patients with M0, non-metastatic CRPC (nmCRPC). At GU ASCO 2018, both PROSPER 1 and SPARTAN 2 presented results of their phase III trials – both presenting metastases-free survival (MFS) as the primary endpoint. 
Presented by Teuvo Tammela, MD, PhD
Barcelona, Spain (UroToday.com)  Dr. Teuvo Tammela presented results of the recently published ARAMIS trial. Non-metastatic (M0) CRPC (nmCRPC) is defined as a rising PSA in the setting of non-metastatic disease in the castrate state.
Presented by Karim Fizazi, MD, Ph.D.
San Francisco, CA (UroToday.com) The treatment landscape for non-metastatic castration-resistant prostate (nmCRPC) cancer is rapidly evolving. In 2018, Enzalutamide (July 2018) and Apalutamide (February 2018) became the first two drugs to obtain FDA approval for the treatment of nmCRPC. SPARTAN was a phase 3 double-blind, randomized study of apalutamide versus placebo in patients nmCRPC.
Presented by Ian D. Davis, MBBS, Ph.D.
San Francisco, CA (UroToday.com) Dr. Ian Davis provided a discussion of the 3 positive clinical trials just presented – LATITUDE (final results), ARAMIS, and ARCHES. He did start by noting his conflicts of interest, particularly that he is an advisor for many of the companies – but also, that as an Australian, he is a believer in affordable universal health care (and cost-effective healthcare delivery).
Presented by Karim Fizazi, MD, PhD
San Francisco, CA (UroToday.com) The use of androgen-axis targeted agents, specifically enzalutamide and abiraterone, have drastically changed the landscape of advanced prostate cancer management. Just last year, at GU ASCO 2018,