Multinational phase 3 trial of perioperative apalutamide in high-risk localized prostate cancer

Radical prostatectomy is potentially curative in patients with high-risk localized or locally advanced prostate cancer; however, relapse occurs within 5 years in up to 50% of patients. The multinational phase 3 PROTEUS trial evaluated perioperative apalutamide for these patients. Particpants with newly diagnosed high-risk localized or locally advanced prostate cancer were randomized 1:1 to receive androgen deprivation therapy (ADT) plus apalutamide (n=1057) or ADT plus placebo (n=1052) for six 28-day cycles before and after radical prostatectomy with pelvic lymph-node dissection. The dual primary endpoints were a composite of pathological complete response or minimal residual disease (pathological stage of ypT2 or lower, with a tumor size of ≤ 5 mm in the greatest dimension) and metastasis-free survival. The median follow-up was 61.7 months. The percentage of patients with pathological complete response was 8.9% in the apalutamide group versus 1.0% in the placebo group (OR 10.17; p<0.001), as was the percentage of patients with metastasis-free survival (HR 0.80; p=0.02). Event-free survival, time to first subsequent treatment, and time to distant metastasis significantly favored ADT plus apalutamide over ADT plus placebo (p<0.001 for all comparisons). Grade 3 or 4 adverse events occurred in 39.6% of patients in the apalutamide group and 31.0% in the placebo group. The authors conclude that perioperative treatment with ADT plus apalutamide was associated with better oncologic outcomes of radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer than treatment with ADT plus placebo.