Johnson & Johnson: Perioperative ERLEADA plus ADT cuts recurrence or death by 62% vs surgery alone in high-risk prostate cancer

Trial results

The randomized PROTEUS substudy (408 patients) compared perioperative apalutamide plus androgen deprivation therapy (ADT) with radical prostatectomy alone in newly diagnosed, non‑metastatic high‑risk or locally advanced prostate cancer. At median follow‑up of 37.8 months, apalutamide plus ADT reduced the risk of recurrence or death by 62% (HR 0.38; 95% CI 0.26–0.55; p<0.0001). Median event‑free survival (EFS) was not reached with the investigational regimen versus 19.1 months with surgery alone; three‑year EFS was 63% versus 41.4%.

Secondary and exploratory endpoints

Apalutamide plus ADT showed a 51% lower risk of distant metastasis or death for metastasis‑free survival (HR 0.49; 95% CI 0.26–0.90; nominal p=0.0193). Time to first subsequent systemic therapy favored the perioperative regimen (HR 0.29), with 64.6% versus 32% free from subsequent therapy at three years. Additional follow‑up is ongoing for overall survival.

Design, safety and regulatory context

Patients received apalutamide 240 mg daily for six 28‑day cycles before and six cycles after surgery, with a planned pause two weeks before and restart four weeks after prostatectomy. Grade 3–4 treatment‑emergent adverse events occurred in 31% versus 22%. No treatment‑emergent deaths were reported. Apalutamide is approved in advanced prostate cancer but is not approved for high‑risk localized or locally advanced disease.