apalutamide in high-risk localized prostate cancer

Apalutamide is an oral non-steroidal anti-androgen. Apalutamide binds to the ligand-binding domain of the androgen receptor (AR) with seven- to 10-fold greater affinity compared with bicalutamide (1).

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 (2).

In a double-blind, placebo-controlled trial in which patients with newly diagnosed high-risk localized or locally advanced prostate cancer (2):

• dual primary end points were a composite of pathological complete response or minimal residual disease (defined as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension) and metastasis-free survival, as assessed with conventional imaging or prostate-specific membrane antigen positron-emission tomography
• found androgen-deprivation therapy (ADT) plus apalutamide linked to greater success of radical prostatectomy than treatment with ADT plus placebo (pathological complete response or minimal residual disease in 8.9% vs. 1.0%; OR 10.17; 95% CI, 5.27 to 19.64; P<0.001) and an increased percentage of patients with metastasis-free survival (probability of metastasis-free survival at 5 years, 78.2% vs. 73.5%)
• grade 3 or 4 adverse events occurred in 39.6% of the patients in the apalutamide group and in 31.0% of those in the placebo group, with the difference between the groups driven primarily by a higher incidence of rash in the apalutamide group

The study authors concluded (2):

“..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. Adverse events were more common in the apalutamide group than in the placebo group…”

Reference:

1. Rathkopf DE, Scher HI. Apalutamide for the treatment of prostate cancer. Expert Rev Anticancer Ther. 2018 Sep;18(9):823-836.
2. Taplin ME et al; PROTEUS Investigators. Perioperative Apalutamide in High-Risk Localized Prostate Cancer. N Engl J Med. 2026 May 31.