Risk of therapy-related adverse events in men on abiraterone or enzalutamide, a meta-analysis of clinical trial data

Lead Investigator: Grace Lu-Yao, Thomas Jefferson University
Title of Proposal Research: Risk of therapy-related adverse events in men on abiraterone or enzalutamide, a meta-analysis of clinical trial data
Vivli Data Request: 8688
Funding Source: All of Amy Shaver’s research is supported in part by NCI Cancer Center Support Grant 5P30CA056-036
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Background: Prostate cancer (PCa) is the most common cancer and second leading cause of death among men; over 260,000 men are diagnosed yearly and nearly 35,000 will die from the disease. Patients receive first generation androgen deprivation therapy. First-generation androgen deprivation therapy (ADT) blocks the secretion of testosterone and other androgens and is first-line therapy. PCa requires testosterone (an androgen) in order to grow, by depriving the body of the androgen testosterone (the male sex hormone) ADT may slow the cancer’s growth and temporarily shrink the cancer. However, PCa patients are at increased risk of therapy-related adverse events (AEs), including cardiovascular disease (CVD) outcomes. The introduction of newer agents called androgen receptor targeted (ART) drugs to ADT may further increase therapy-related AE and CVD risk. ARTs work in two ways, either by blocking the site (androgen receptor) on the tumor so it cannot receive androgens (enzalutamide) depriving the tumor of androgens or by blocking androgen synthesis (abiraterone); both means decrease a tumor’s ability to grow. There is no clear recommendation in clinical guidelines to recommend one drug over the other, and the choice of treatment options complicates clinical decision-making. This trial will conduct a comparative analysis using established statistical methods and develop guidance from this analysis to aid clinician decision-making and thereby enhancing patient care. Is there a difference in outcomes according to patient type based on drug received? Alternatively, are the outcomes similar for all patients regardless of drug choice?

Requested Studies:

A Phase I, Open-label, Dose-finding Study of GSK2636771 Administered in Combination With Enzalutamide (Xtandi^TM ) in Male Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Data Contributor: GSK
Study ID: NCT02215096
Sponsor ID: 200331

A Randomized, Open Label, Multicenter Study of Cabazitaxel Versus an Androgen Receptor (AR)-Targeted Agent (Abiraterone or Enzalutamide) in mCRPC Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)
Data Contributor: Sanofi
Study ID: NCT02485691
Sponsor ID: LPS14201

A Phase I/II Open Label Study of the 17α-Hydroxylase/ C17,20 Lyase Inhibitor, Abiraterone Acetate in Patients With Prostate Cancer Who Have Failed Hormone Therapy
Data Contributor: Johnson & Johnson
Study ID: NCT00473512
Sponsor ID: CR016909

Phase I/II Open Label Dose Escalation Study of the 17α-Hydroxylase/ C17,20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer
Data Contributor: Johnson & Johnson
Study ID: NCT00473746
Sponsor ID: CR016969

A Phase II Open Label Study of CB7630 (Abiraterone Acetate) in Patients With Advanced Prostate Cancer Who Have Failed Androgen Deprivation and Docetaxel-Based Chemotherapy
Data Contributor: Johnson & Johnson
Study ID: NCT00474383
Sponsor ID: CR016915

An Observational Study of Continuous Oral Dosing of an Irreversible CYP17 Inhibitor, Abiraterone Acetate (CB7630), in Castration-Resistant Prostate Cancer Patients Evaluating Androgens and Steroid Metabolites in Bone Marrow Plasma
Data Contributor: Johnson & Johnson
Study ID: NCT00544440
Sponsor ID: CR016906

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy
Data Contributor: Johnson & Johnson
Study ID: NCT00638690
Sponsor ID: CR016924

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer
Data Contributor: Johnson & Johnson
Study ID: NCT00887198
Sponsor ID: CR016927

A Phase 2 Open-Label, Randomized, Multi-center Study of Neoadjuvant Abiraterone Acetate (CB7630) Plus Leuprolide Acetate and Prednisone Versus Leuprolide Acetate Alone in Men With Localized High Risk Prostate Cancer
Data Contributor: Johnson & Johnson
Study ID: NCT00924469
Sponsor ID: CR016936

A Randomized, Open-Label, Neoadjuvant Prostate Cancer Trial of Abiraterone Acetate Plus LHRHa Versus LHRHa Alone
Data Contributor: Johnson & Johnson
Study ID: NCT01088529
Sponsor ID: CR016945

A Multicenter, Open-label, Single-arm, Phase 2 Study of Abiraterone Acetate Plus Prednisone in Subjects With Advanced Prostate Cancer Without Radiographic Evidence of Metastatic Disease
Data Contributor: Johnson & Johnson
Study ID: NCT01314118
Sponsor ID: CR017932