ERLEADA - PROTEUS Study

SUMMARY

• PROTEUS (NCT03767244) is a phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of 12 cycles of perioperative treatment with ERLEADA plus androgen deprivation therapy (ADT; n=1057) compared with placebo plus ADT (n=1052) in patients with newly diagnosed localized or locally advanced high-risk prostate cancer undergoing radical prostatectomy (RP) with pelvic lymph-node dissection (N=2109). Patients were enrolled across 184 sites in 18 countries. The dual primary endpoints are a composite endpoint of pathological complete response (pCR) or minimal residual disease (MRD) and metastasis-free survival (MFS), based on conventional or prostate-specific membrane antigen positron-emission tomography (PSMA-PET) imaging. Both endpoints were assessed by blinded independent central review (BICR).^1-3
  • After a median follow-up of 61.7 months, the percentage of patients with a pCR or MRD was significantly higher in the ERLEADA group vs the placebo group (8.9% vs 1.0%; odds ratio [OR], 10.17; 95% confidence interval [CI], 5.27-19.64; P<0.001) as well as probability of MFS at 5 years (78.2% vs. 73.5%; hazard ratio [HR], 0.80; 95% CI, 0.67-0.96; P=0.02).
  • The secondary endpoints of event-free survival (median, 57.1 months vs 38.4 months; HR, 0.71; 95% CI, 0.63-0.80), time to the first subsequent treatment (median, 74.2 months vs 41.5 months; HR, 0.65; 95% CI, 0.57-0.73), and time to distant metastasis detected on conventional or PSMA-PET imaging (median not reached in either treatment arm; HR, 0.68; 95% CI, 0.55-0.83) were also significant for the ERLEADA group vs the placebo group (P<0.001 for all between-group comparisons) as did the proportion of patients with no evidence of disease at 4 years (21.9% vs 18.3%; OR, 1.25; 95% CI, 1.01-1.55; P=0.04).
  • Any adverse event (AE) occurred in 98.8% vs 97.8% of patients in the ERLEADA group vs placebo group, with grade 3 or 4 AEs occurring in 39.6% vs 31.0%, respectively. The most common AEs in the ERLEADA group vs placebo group were: hot flush (63.4% vs 56.5%), urinary incontinence (50.2% vs 50.9%), erectile dysfunction (41.6% vs 41.4%), fatigue (27.7% vs 26.8%), arthralgia (22.6% vs 19.4%), and rash (21.2% vs 10.0%).
• A PROTEUS substudy is ongoing to compare ERLEADA plus ADT plus RP vs RP alone.
• The infographic below provide an overview of the study design, efficacy, and safety results.

CLINICAL DATA

PROTEUS Study

PROTEUS is a phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of ERLEADA plus ADT compared to placebo plus ADT before and after RP in patients with localized or locally advanced high-risk prostate cancer (N=2109).¹

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 01 June 2026.