Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302

Abstract

Background: Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P).

Objective: This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (<75 yr) patient subgroups.

Design, setting, and participants: Data were collected at the final OS analysis (96% of expected death events). Subsequent therapy data were prospectively collected, while response and discontinuation data were collected retrospectively following discontinuation of the study drug.

Intervention: At the discretion of the investigator, 67% (365/546) of patients from the AA arm received subsequent treatment with one or more agents approved for mCRPC.

Outcome measurements and statistical analysis: Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available.

Results and limitations: Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients.

Conclusions: Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients.

Trial registration: ClinicalTrials.gov NCT00887198.

Patient summary: Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced prostate cancer whose disease progressed after treatment with abiraterone acetate. Older patients were less likely to be treated with subsequent therapy.

Keywords: Abiraterone acetate; Docetaxel; Elderly; Metastatic castration-resistant prostate cancer; Subsequent therapy; Treatment patterns.

Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

CONSORT diagram. a Abiraterone acetate, cabazitaxel, enzalutamide, ketoconazole, or sipuleucel-T.

Fig. 2

Unconfirmed PSA declines among patients treated with abiraterone acetate who received docetaxel as first subsequent therapy. (A) Maximum PSA decline from baseline. (B) Total and confirmed post-treatment PSA decline. Waterfall plot with maximum PSA change and PSA response rate for patients with available baseline PSA within 30 d of subsequent docetaxel therapy and at least one post-baseline PSA value. PSA = prostate-specific antigen; AA = abiraterone acetate plus prednisone.

Fig. 3

First subsequent therapy by age subgroup. (A) Docetaxel as first subsequent therapy and no subsequent therapy. (B) All first subsequent therapy. AA = abiraterone acetate plus prednisone; P = placebo plus prednisone.