# Comparative evidence: enzalutamide vs abiraterone or other AR pathway inhibitors

## Enzalutamide and abiraterone provide similar overall survival in prostate cancer, but enzalutamide shows modest advantages for progression endpoints in castration-resistant disease, and sequencing from abiraterone to enzalutamide yields better outcomes than the reverse order due to preserved second-line activity.

# Abstract

Ten studies including direct randomized trials, crossover studies, and network meta-analyses compared AR pathway inhibitors across metastatic castration-resistant, hormone-sensitive, and high-risk nonmetastatic prostate cancer settings...

## Methods

We analyzed 10 sources from an initial pool of 200, using 9 screening criteria...

## Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine...

## Screening

We screened in sources based on their abstracts that met these criteria:

- **Population**: Does the study include patients with prostate cancer receiving treatment with AR pathway inhibitors?
- **Enzalutamide Intervention**: Does the study include enzalutamide as one of the interventions being compared?
- **AR Pathway Inhibitor Comparator**: Does the study include abiraterone, apalutamide, darolutamide, or other AR pathway inhibitors as comparator(s)?
- **Comparative Design**: Does the study involve direct head-to-head comparison or indirect comparison through network meta-analysis?  
...

## Results

### Characteristics of Included Studies

The systematic review included 10 studies comparing AR pathway inhibitors in prostate cancer across different disease settings and lines of therapy.

| Study                                  | Full text retrieved? | Study Type      | Sample Size              | Disease Setting                    | Comparison                                                | Follow-up           |
|----------------------------------------|----------------------|------------------|--------------------------|--------------------------------------|-----------------------------------------------------------|----------------------|
| R. de Wit et al., 2019                | No                   | RCT              | 255 (129 cabazitaxel, 126 ARPi) | Metastatic CRPC                   | Cabazitaxel vs abiraterone/enzalutamide                | 9.2 months median    |
| D. Khalaf et al., 2019                | Yes                  | RCT (crossover)  | 202 (101 per arm)       | Metastatic CRPC                   | Abiraterone→enzalutamide vs enzalutamide→abiraterone    | 22.8 months median   |
...

### Overall Survival

Overall survival data showed variable results across different disease contexts and treatment lines...

### Progression-Free Survival

Progression-free survival outcomes varied substantially by disease setting and prior treatment...

### PSA Response and Biochemical Outcomes

PSA response rates demonstrated notable variation across comparisons...

### Tumor Response

Objective tumor response rates were reported in limited studies...

### Safety and Tolerability

Overall adverse event rates showed considerable variation across studies...

## Synthesis

The apparent contradictions in comparative efficacy between enzalutamide and abiraterone can be reconciled by examining context-specific factors.