Enzalutamide Versus Abiraterone as a First-Line Endocrine Therapy for Castration-Resistant Prostate Cancer: Protocol for a Multicenter Randomized Phase 3 Trial

Abstract

BackgroundRecent large-scale randomized studies have demonstrated that 2 new hormone preparations (abiraterone and enzalutamide) prolong survival in docetaxel-treated or -naïve castration-resistant prostate cancer patients. However, no studies have directly compared antitumor effects between these 2 agents, and no clear guidelines are available for choosing between them.ObjectiveThe objective of this clinical study is to compare antitumor effects and adverse events between abiraterone and enzalutamide by allocating castration-resistant prostate cancer patients deemed not indicated for docetaxel treatment to receive either of the 2 agents.MethodsThis study is an open-label, comparative study allocating castration-resistant prostate cancer patients to abiraterone or enzalutamide treatment arms (allocation factors: age <70 vs ≥70 years, and presence vs absence of metastases) and assessing the treatment results. Each arm will contain 25 patients. On confirmation of prostate-specific antigen failure or progression on imaging, patients undergo crossover to receive the alternative study drug. The primary end point is prostate-specific antigen response rate (percentage of patients with a decrease in prostate-specific antigen level by ≥50%) in the abiraterone and enzalutamide treatment arms.ResultsRecruitment started in May 2016, and 13 patients have been recruited so far. We expect to complete enrollment by December 2020.ConclusionsRecently, cross-resistance between abiraterone and enzalutamide has been an issue of focus. Urologists thus tend to prefer docetaxel rather than sequential therapies using 2 hormonal preparations after the progression of a first hormonal preparation. From that perspective, our clinical trial is rather out of fashion. Nevertheless, we assume that many patients receive hormonal sequential therapy in the actual clinical setting, since most such patients cannot receive chemotherapeutic agents due to old age or poor performance status. This is why we are attempting this randomized clinical trial comparing abiraterone versus enzalutamide. We will try to identify which drug is suitable for initial hormonal therapy among castration-resistant prostate cancer patients who do not meet the indications for docetaxel therapy in terms of not only antitumor effect, but also adverse events and quality of life.Trial RegistrationUniversity Hospital Medical Information Network UMIN000022102; https://upload.umin.ac.jp /cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025463 (Archived by WebCite at http://www.webcitation.org/70xaQfGlJ)

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment

“…We also observed that many of the differentially methylated genes overlapped between Enzalutamide- and Abiraterone-treated patients. Although there are ongoing studies to compare efficacy of either treatment (55), the current consensus is that both perform similarly, and deciding between treatments in a patient-specific manner remains an ongoing challenge. We identified sets of genes altered in the promoter and gene body locations, including one large set amongst Enzalutamide treated patients.…”

Enzalutamide versus Abiraterone Acetate as first-line treatment of castration resistant metastatic prostate cancer in geriatric (≥75) patients

“…Unfortunately, there is no study directly comparing the efficacy of AA and ENZA in the first-line setting. There are still ongoing studies [18,19].…”

Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

“…However, to our knowledge, no head-to-head randomized, controlled trial has compared these two medications, except Khalaf and colleagues’ work which aimed at comparison of sequences of medications. Hara et al (2018) designed a study protocol for a multicenter, randomized, phase 3 trial to compare these two medications. The results of this trial are still pending.…”