Enzalutamide and Abiraterone Improved Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer

27 Nov, 18

Introduction

Prostate cancer that has progressed after initial androgen deprivation therapy (ADT) is referred to as castration-resistant prostate cancer (CRPC). Although ADT is effective in a majority of the patients with advanced prostate cancer, CRPC develops in almost all the patients after 12-18 months of the therapy. Targeted therapy is a new treatment modality for metastatic CRPC (mCRPC). However, the data on efficacy and tolerability of the targeted agents is limited. There is no network meta-analyses which compares the efficacy of various targeted agents in patients with mCRPC.

Aim

To evaluate the efficacy and tolerability of various targeted agents in mCRPC using network meta-analyses.

Method

Study Design

Network meta-analyses was performed in accordance with the Preferred Reporting Items for Systematic Reviews Statement for Network Meta-analyses (PRISMA-NMA) guidelines.

Treatment Strategy

Databases of MEDLINE, EMBASE and the Cochrane Library were searched
Randomized controlled trials (RCTs) with blinded design, in which patients having mCRPC were treated with targeted agents and the control group received another type of targeted agents or placebo were included
The RCTs included studies which assessed the survival outcomes

Endpoints

Progression-free survival (PFS) defined as the length of time between random assignment of patients and occurrence of events
Overall survival (OS) defined as time from randomization to death from any cause
Tolerability outcome were severe adverse events (AEs) of grade >3

Results

A total of 26 studies comprising of 20,314 patients were assessed
Random-effect analysis demonstrated a significant prolonged PFS by the targeted agents (I²=94.3%; HR 0.74; p<0.001), irrespective of whether the patients had received chemotherapy.
The surface under the cumulative ranking curve (SUCRA) findings revealed that enzalutamide was the most effective in improving the PFS of mCRPC patients (100%) followed by abiraterone ((90.1%) and tasquinimod (84.2%)

The OS was also significantly prolonged by the targeted agents (I²=71.6%; HR 0.91; p<0.001)

SUCRA analysis showed that enzalutamide was the most effective in improving the OS of mCRPC patients (97.2%) followed by abiraterone (91.1%) and zibotentan (65.8%)

The incidence of severe AEs were lowest with intetumumab (94.9%), followed by atrasentan (85.1%) and placebo (79.3%)

Conclusion

Enzalutamide was the most effective in prolonging the PFS, followed by abiraterone and tasquinimod in patients with mCRPC.
The OS was better in patients treated with enzalutamide and abiraterone
Both these drugs not only improved the survival outcomes but also were also associated with a low incidence of severe AEs.

J Cancer Res Clin Oncol. 2018 Sep;144(9):1751-1768. Doi: 10.1007/s00432-018-2664-y.