Efficacy of Enzalutamide Following Abiraterone Acetate in Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer Patients

Abstract

Background

The activity of enzalutamide after prior treatment with both abiraterone acetate (abiraterone) and docetaxel has been examined in several retrospective studies. However, limited data are available on the efficacy of enzalutamide following abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).

Objective

To compare the activity of enzalutamide after abiraterone in docetaxel-experienced and docetaxel-naive mCRPC patients.

Design, setting, and participants

The British Columbia Cancer Agency Cancer Registry was searched for mCRPC patients who received enzalutamide after prior abiraterone. Clinicopathologic characteristics, confirmed prostate-specific antigen (PSA) response rates (PSA decline ≥50% confirmed ≥3 wk later), and survival data were collected.

Outcome measurements and statistical analysis

Outcomes on enzalutamide were compared between docetaxel-experienced and docetaxel-naive patients using chi-square for PSA response and log-rank test for time to PSA progression and overall survival (OS). Univariate analysis was performed to identify variables associated with confirmed PSA response on enzalutamide, using either chi-square for categorical variables or logistic regression for continuous variables.

Results and limitations

A total of 115 patients received enzalutamide after abiraterone: 68 had received prior docetaxel and 47 were docetaxel naive. Median time on enzalutamide was 4.1 mo. Confirmed PSA response rates (22% vs 26%; p = 0.8), median time to radiologic/clinical progression (4.6 mo vs 6.6 mo; p = 0.6), and median OS (10.6 mo vs 8.6 mo; p = 0.2) did not differ significantly between docetaxel-experienced and docetaxel-naive patients. No clinical variables (including prior response to abiraterone) were found to associate significantly with confirmed PSA response to enzalutamide.

Conclusions

Antitumour activity of enzalutamide following abiraterone was limited in mCRPC patients irrespective of prior docetaxel use. Identifying clinical and molecular factors predictive of response to enzalutamide remains a high priority for future research.

Patient summary

We looked at the effectiveness of enzalutamide after abiraterone acetate for treatment of advanced prostate cancer. We found that patients who had received docetaxel chemotherapy before abiraterone gained similar benefit from enzalutamide compared with patients who had not received docetaxel. These results suggest that earlier treatment with docetaxel does not have a large impact on the activity of enzalutamide after abiraterone.

Introduction

The therapeutic armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has rapidly expanded in recent years with several novel agents demonstrating a benefit on overall survival (OS) [1]. Among these agents are the novel androgen receptor (AR)-targeted therapies abiraterone acetate (abiraterone) and enzalutamide that inhibit CYP17 and AR, respectively. Both abiraterone and enzalutamide are increasingly being used in chemotherapy-naive mCRPC patients on the basis of positive data from the COU-AA-302 (abiraterone) and PREVAIL (enzalutamide) phase 3 studies [2], [3]. Despite their efficacy, however, many questions regarding the use of abiraterone and enzalutamide remain unanswered including the optimal sequencing of treatment. Several prior studies have reported on outcomes in mCRPC patients treated with enzalutamide after abiraterone [4], [5], [6], [7], [8], [9]. All but one of these studies [9] were restricted to patients previously treated with docetaxel, and currently little is known about the activity of enzalutamide following abiraterone in docetaxel-naive mCRPC patients. The aim of this study was to examine the activity of enzalutamide after abiraterone in mCRPC patients not previously treated with docetaxel chemotherapy and to compare outcomes with docetaxel-experienced patients.