Apalutamide for High-Risk Localized Prostate Cancer Following Radical Prostatectomy (Apa-RP)

J Urol. 2024 Nov;212(5):682-691. doi: 10.1097/JU.0000000000004163. Epub 2024 Aug 1.

Abstract

Purpose: Approximately 25% to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence (BCR) within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy (ADT) in high-risk patients who have undergone radical prostatectomy improved BCR-free survival.

Materials and methods: Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the US. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus ADT. The primary end point was BCR-free survival. Secondary end points included testosterone recovery (≥150 ng/dL) and safety.

Results: One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0 years). Median preoperative PSA and baseline testosterone were 7.6 ng/mL (range 2.2-62.7 ng/mL) and 340.0 ng/dL (range 43.0-939.0 ng/dL), respectively. The BCR-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events.

Conclusions: In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy.

Trial registration: ClinicalTrials.gov Identifier: NCT04523207.

Keywords: apalutamide; high-risk; localized prostate cancer; radical prostatectomy.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Androgen Antagonists* / administration & dosage
  • Androgen Antagonists* / therapeutic use
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen / blood
  • Prostatectomy* / methods
  • Prostatic Neoplasms* / blood
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / surgery
  • Testosterone / blood
  • Thiohydantoins* / administration & dosage
  • Thiohydantoins* / therapeutic use

Substances

  • apalutamide
  • Thiohydantoins
  • Androgen Antagonists
  • Prostate-Specific Antigen
  • Testosterone

Associated data

  • ClinicalTrials.gov/NCT04523207