SPARTAN, PROSPER and ARAMIS: 2020 Update

Non-metastatic castration-resistant prostate cancer (nmCRPC) affects at least 110,000 patients in the United States each year, comprises 1% to 2% of prostate cancers worldwide, and is a significant risk factor for progression to overt metastatic disease and cancer-related death.1,2 Amidst the many challenges of 2020, a bright spot has been the reporting of final overall survival (OS) data from the registrational SPARTAN, PROSPER, and ARAMIS trials, which confirm that for appropriately selected patients with high-risk nmCRPC, treatment with a next-generation androgen receptor (AR) inhibitor, whether apalutamide, enzalutamide, or darolutamide, significantly prolongs both metastasis-free survival (MFS) and overall survival (OS). It is remarkable that we now have three approved therapies for a disease state wherein, just three years ago, there was no level 1 evidence for an approved therapeutic. Herein, I will review the new efficacy and safety data and clinical implications for these recently approved nmCRPC agents.

The Efficacy of Darolutamide for Non Metastatic Castration-Resistant Prostate Patients

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.

An Update on Nonmetastatic Castration-Resistant Prostate Cancer

Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer patients who have failed primary interventional therapy.  Most of these patients will develop, through a potential multitude of resistance mechanisms, neoplastic cellular progression, and proliferation which subsequently leads to PSA relapse.2 Castration-resistant prostate cancer (CRPC), a rising PSA with castrate levels of testosterone alongside no radiographic imaging findings with conventional imaging (CT/Bone scans) are designated as non-metastatic (nmCRPC), or sometimes as M0CRPC.

From the Desk of the Editor

Welcome to the timely new nmCRPC prostate cancer (nmCRPC) Center of Excellence.

Until February 2018 and the milestone ASCO GU presentations of the Phase III trials, A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer (SPARTAN) and Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (PROSPER),