Apa-RP: Phase 2 Study of Apalutamide and Androgen-Deprivation Therapy (ADT) in Treatment-Naive Patients Post-Radical Prostatectomy (RP) for Nonmetastatic Prostate Cancer at High Risk for Metastases
Although RP is a standard treatment for high-risk prostate cancer (PC), disease recurrence rate post-RP is 40%-75% (D’Amico et al. 1993; Stephenson et al. 2006; Murata et al. 2018), with recurrence leading to PC-related mortality. Adjuvant radiotherapy may be beneficial but is used inconsistently (Vargas et al. 2005). Intensified androgen receptor (AR) blockade in early disease prior to RP has been demonstrated to reduce tumor burden post-RP (Taplin et al. 2014) and evidence exists supporting adjuvant ADT in patients with node-positive PC (Messing et al. 2006). Apalutamide is an AR inhibitor approved for the treatment of metastatic castration-sensitive PC and nonmetastatic castration-resistant PC. The Apa-RP study (ClinicalTrials.gov identifier: NCT04523207) will evaluate whether adjuvant treatment with apalutamide and ADT post-RP improves the biochemical recurrence (BCR)-free rate in patients with treatment-naive nonmetastatic PC at high risk for development of metastases.
This is an open-label, single-arm study in patients (N=94) with localized high-risk nonmetastatic PC in ≈30 US urology sites. High-risk definition: PSA ≥20 ng/mL; or Gleason score (GS) ≥9 (any core); or GS ≥8 (>80% of 2 cores); or GS=8 (1 core w/≥5 cores [minimum GS 4+3]) from biopsy or equivalent from RP specimen. Patients post-RP recovered from surgery with PSA ≤0.2 ng/mL will receive apalutamide 240 mg/d and ADT (investigator’s choice) for 12 months. The primary endpoint is BCR-free rate at 24 months. Secondary endpoints include BCR-free rate at 12 months, and 18- and 24-month testosterone recovery rate. PSA, testosterone, and safety will be monitored. A substudy (n=12) will examine coadministration of apalutamide with relugolix (primary endpoint: castrate testosterone levels through Day 28). Study recruitment began August 2020. As of 30 June 2021, 61 patients were screened, and 43 patients are enrolled, including 12% Black patients.
Hafron JM, Saltzstein DR, Lacouture ME, Sutton J, Potdar R, Bhaumik A, Phillips J, McGowan T, Shore ND. Apa-RP: phase 2 study of apalutamide and androgen-deprivation therapy (ADT) in treatment-naive patients post-radical prostatectomy (RP) for nonmetastatic prostate cancer at high risk for metastases. Paper presented at: The 22nd Annual National Meeting of the Society of Urologic Oncology; 2021 Dec 1-3; Orlando, Florida.