The Efficacy and Safety of Abiraterone Acetate in Patients With High-Risk Prostate Cancer

A Meta-Analysis Based on Six Randomized Control Trials

Guobin Tan; Zijun Xuan; Zhiqin Li; Shuitong Huang; Guangming Chen; Yonglu Wu; Xianxi Chen; Zhijin Liang; Aiming Wu

Disclosures

Transl Androl Urol. 2020;9(4):1691-1699. 

In This Article

Abstract and Introduction

Abstract

Background: Abiraterone acetate, a CYP17 enzyme inhibitor, can block the synthesis of androgens in the adrenal gland, prostate, and testis. The purpose of this study was to investigate the efficacy and safety of abiraterone acetate in high-risk prostate cancer patients, including metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

Methods: A meta-analysis based on 6 randomized controlled trials (RCTs) was undertaken in compliance with the guidelines of systematic reviews and meta-analyses. Databases including PubMed, EMBASE, and Cochrane library were searched for relevant literature through to September 2019.

Results: The pooled analysis reported abiraterone acetate showed significant efficacy in high-risk prostate cancer patients, including overall survival (OS) [HR 0.66, 95% confidence interval (CI), 0.61–0.73, P<0.001], the time to prostate-specific antigen (PSA) progression (HR 0.45, 95% CI, 0.34–0.59, P<0.001), progression-free survival (PFS) (according to radiographic evidence) (HR 0.55, 95% CI, 0.45–0.68, P<0.001) and PSA response rate (RR 2.49, 95% CI, 1.47–4.22, P<0.001). A subgroup analysis was carried out due to the significant heterogeneity between the studies. The incidence of arthralgia (RR 1.19), hypokalemia (RR 2.47), cardiac disorder (RR 1.48), and hypertension (RR 1.57) in the abiraterone acetate group was moderately higher than the control group.

Conclusions: The efficacy and safety of abiraterone acetate as an androgen receptor (AR) pathway targeted drug in high-risk prostate cancer patients was confirmed.

Introduction

In Europe and America, prostate cancer is the most common urogenital cancer.[1] In America, about 3% of prostate cancer patients are diagnosed with metastatic castration-sensitive prostate cancer (mCSPC). The conventional treatment for mCSPC is androgen deprivation therapy (ADT), which includes luteinizing hormone-releasing hormone analogs, bilateral testicular resection, or first-generation androgen receptor (AR) blocker. Also, this standard treatment strategy has been proposed for this kind of patient for a long time.[2] Although most patients have an initial response to ADT, within about a year, the majority progress to become castration-resistant prostate cancer (CRPC).[3,4] AR signaling promotes CRPC primarily through up-regulation of testosterone production in tumors, sustained production of adrenal androgen, parallel pathways of steroid production, and changes to biological characteristics of ARs.[2] New endocrine drugs for the treatment of CRPC include enzalutamind and abiraterone acetate. In addition, cytotoxic drugs and immunotherapeutic drugs such as docetaxel, cabazitaxel, mitoxantrone, estramustine, and Sipuleucel-T are also used to treat CRPC. Abiraterone acetate, a CYP17 enzyme inhibitor, can block the synthesis of androgen in the adrenal gland, prostate, and testis.[5] Several high-quality randomized controlled trials (RCTs) have stated that abiraterone acetate plus prednisone (AAP) achieved significant efficacy in high-risk prostate cancer patients, including castration-resistant and castration-sensitive, and also provided additional clinical benefits.[6–17] Previous studies[18–20] have also demonstrated the efficacy and safety of abiraterone acetate in high-risk prostate cancer patients. However, the difference in efficacy of abiraterone acetate between metastatic castration-resistant prostate cancer (mCRPC) and mCSPC remains unclear, as does whether earlier use of abiraterone acetate in mCSPC could improve clinical benefits. In this meta-analysis, we aimed to investigate the efficacy of abiraterone acetate in mCRPC and mCSPC based on 6 RCTs. We present the following article in accordance with the PRISMA reporting checklist (available at http://dx.doi.org/10.21037/tau-20-1058).

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