Prevail Trial

Background

Phase III double-blind RCT; 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC), asymptomatic or minimally symptomatic. Patients with history of seizure excluded unless on antiseizure medication.

Interventions and follow up

Arm A: Enzalutamide 160mg daily + ADT.
Arm B: Placebo + ADT.
Primary endpoints: OS and radiographic PFS.
mFollow up: 22mo (primary); 69mo (final OS analysis).

Results

mOS (interim): 32.4mo vs 30.2mo, arm A vs B; HR 0.71, 95%CI 0.60–0.84; P<.001.
12mo PFS: 65% vs 14%, arm A vs B; HR 0.19, 95%CI 0.15–0.23; P<.001.
mPFS: 20.0mo vs 5.4mo, arm A vs B; HR 0.32, 95%CI 0.28–0.37; P<.001.
mOS (final, 69mo): 35.5mo vs 31.4mo, arm A vs B; HR 0.83, 95%CI 0.75–0.93; P<.001.

Adverse events

Overall: Grade 3–4 events 43% vs 37% (arm A vs B).
Common: Hypertension 7% vs 2%; plus hot flush, falls, and atrial fibrillation (2% vs 1%) more frequent with enzalutamide.

Conclusions

Enzalutamide + ADT improved OS and radiographic PFS, delayed need for chemotherapy, and preserved quality of life in chemotherapy-naive, minimally symptomatic mCRPC versus ADT alone.

Key Limitations

Placebo comparator (no active control); pre-docetaxel mCRPC population, so does not inform optimal sequencing of androgen-receptor agents versus taxanes or use after prior abiraterone.

Clinical Context

FDA expanded enzalutamide to the pre-chemotherapy mCRPC setting in 2014 based on PREVAIL. Endorsed by ASCO/ESMO as a standard option for chemotherapy-naive mCRPC.

References

Tomasz MB et al, NEJM, 2014; PMID: 24881730
Beer TM et al. Eur Urol, 2017; PMID:27477525
Armstrong AJ et al. Eur Urol, 2020; PMID:32527692