The management of high-risk localized and locally advanced prostate cancer remains challenging, as a substantial proportion of patients experience disease recurrence despite definitive local therapy. Radical prostatectomy alone is often insufficient in this population, with a substantial proportion of patients ultimately experiencing disease recurrence or progression.
The PROTEUS trial (NCT03767244) was designed to address this gap by evaluating whether adding apalutamide, a potent androgen receptor inhibitor, to androgen deprivation therapy (ADT) in the neoadjuvant and adjuvant settings could improve pathologic complete response or minimal residual disease and metastasis-free survival in high-risk localized or locally advanced prostate cancer.
In this study, 2109 patients were randomized 1:1 to receive perioperative apalutamide plus ADT or placebo plus ADT, given before and after surgery. At a median follow-up of 61.7 months, the addition of apalutamide significantly improved both primary endpoints. Rates of pathologic complete response or minimal residual disease were markedly higher with apalutamide plus ADT than with ADT plus placebo (8.9% vs 1.0%; odds ratio, 10.17), representing nearly a 9-fold absolute improvement in pathologic response.
In addition, metastasis-free survival was significantly improved, with perioperative apalutamide plus ADT reducing the risk of distant metastasis or death by 20% compared with ADT plus placebo (hazard ratio, 0.80). Overall survival data remain immature.
Five-year metastasis-free survival rates were 78.2% and 73.5%, respectively. Improvements were also observed across multiple secondary end points, including event-free survival and time to subsequent therapy.
Rates of grade 3 to 4 treatment-emergent adverse events were comparable between arms (apalutamide plus ADT, 39.6% vs ADT plus placebo, 31.0%), and treatment discontinuation due to toxicity was relatively low (7.4% vs 2.7%, respectively).
Ultimately, the results of PROTEUS may support perioperative apalutamide plus ADT as a potential new treatment option for patients with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy.
Source: Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): Final analysis of the PROTEUS phase 3 study. Presented at: ASCO Annual Meeting. May 29-June 2, 2026; Chicago, IL. Abstract LBA1.