SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 299,010 new cases of prostate cancer will be diagnosed in 2024 and 35,250 men will die of the disease.
The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. The major source of PSA (Prostate Specific Antigen) is the prostate gland, and the PSA levels are therefore undetectable within 6 weeks after Radical Prostatectomy. Similarly, following Radiation Therapy there is a gradual decline in PSA, before reaching a post treatment nadir. A detectable PSA level after Radical Prostatectomy, or a rising PSA level following Radiation Therapy is considered PSA failure or biochemical recurrence. The American Urological Association suggested that a PSA of 0.2 ng/mL or higher after Radical Prostatectomy, defines PSA failure or relapse. A PSA rise 2 ng/ml or more above post Radiation Therapy nadir is considered PSA failure or relapse. Approximately 35% of the patients with prostate cancer will experience PSA only relapse within 10 years of their primary treatment and a third of these patients will develop documented metastatic disease within 8 years following PSA only relapse. Rising PSA is therefore a sign of recurrent disease. Patients with biochemically relapsed prostate cancer following local therapy, and a short PSA doubling time, are at risk for distant metastases.
It is estimated that approximately 15-20% of prostate cancer patients are classified as high-risk (PSA 20 ng/mL or more; or Gleason score 8-10; or clinical stage T3 or more). Approximately, 45-65% of patients with high-risk disease have recurrent disease within five years of undergoing Radical Prostatectomy.
ERLEADA® (Apalutamide) is an orally administered Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. Apalutamide is presently approved for the treatment of patients with metastatic Castration Sensitive Prostate Cancer and non-metastatic Castration Resistant Prostate Cancer
Apa-RP is a multicenter, open-label, single-arm, Phase II study, which included 108 patients across 32 U.S. community urologic practices, and investigated the benefit of Apalutamide plus ADT adjuvant to Radical Prostatectomy, in patients with high-risk localized prostate cancer. Key inclusion criteria were high risk localized prostate cancer with a post-radical prostatectomy PSA of 0.2 ng/mL or less. Patients were treatment-naïve, had undergone Radical Prostatectomy, and were treated with Apalutamide 240 mg, orally once daily, every 28 days for 12 cycles along with ADT for 12 months. The median age was 66 years, 14% were African American and about 60% of patients had prostate cancer with a Gleason Score 9-10. The median preoperative PSA was 7.6 ng/mL and median testosterone level was 340 ng/dL. The Primary endpoint evaluated Biochemical Recurrence (BCR)-free rate, defined as two sequential PSA levels of 0.2 ng/mL or less, at 24 months. The Secondary endpoints included testosterone recovery rate to 150 ng/dL or more at 18 and 24 months, as well as Safety.
The study met its Primary endpoint, showing that patients who received 12 months of Apalutamide plus ADT adjuvant to Radical Prostatectomy experienced 100% biochemical recurrence-free survival (RFS) rate at 24 months, with no confirmed biochemical recurrence at 2 plus years following Radical Prostatectomy. The treatment regimen demonstrated a serum testosterone recovery (150 ng/dL or more) rate of 76.4% at 12 months following treatment completion. The safety profile of Apalutamide with ADT was consistent with previous reports and Adverse Events were reported by 99.1% of patients. Adverse Events led to treatment discontinuation in 10.2% of patients and dose reduction or interruption in 13%.
Based on the results of this study, it was concluded that treatment intensification with 12 cycles of Apalutamide and Androgen Deprivation Therapy following Radical Prostatectomy could become an option for patients with high-risk localized prostate cancer.
Apalutamide for high-risk localized prostate cancer following radical prostatectomy (Apa-RP): a multicenter, open-label, single-arm phase 2 study. Shore N, Hafron J, Saltzstein D, et al. Presented at: 2024 American Urological Association Meeting; May 3-May 6, 2022; San Antonio, TX. Abstract P2-07.
