Genitourinary (Prostate) Cancer
A phase 3 study of androgen annihilation in high-risk biochemically relapsed prostate cancer: An Alliance Foundation trial (AFT-19).
Background: Men with biochemically relapsed prostate cancer (BRPC) following prior radical prostatectomy (RP) and a short PSA doubling time (PSADT) are at high risk for the development of metastatic disease and prostate cancer-related mortality. Intermittent androgen deprivation therapy (ADT) is a commonly applied treatment in this disease setting, but fails to achieve prolonged progression-free and treatment-free intervals for the majority of patients (pts). Apalutamide is a next generation androgen receptor (AR) antagonist that has efficacy in non-metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate, a prodrug of the CYP17 androgen synthesis inhibitor abiraterone, has been shown to prolong survival in both CRPC and metastatic hormone-sensitive prostate cancer. We hypothesize that the addition of apalutamide with or without abiraterone acetate/prednisone, as compared to ADT alone, will prolong disease suppression and potentially eradicate micrometastatic disease with a finite duration of treatment in pts with BRPC. Methods: AFT-19 is a randomized, open-label, three arm phase 3 study (first patient enrolled March 2017) of a) degarelix monotherapy compared to each of two experimental arms: b) degarelix plus apalutamide, and c) degarelix plus apalutamide plus abiraterone acetate/prednisone, in pts with BRPC following prior RP without metastases on conventional imaging, and a PSADT of ≤ 9 months. Pts are treated for up to 52 weeks in the absence of progression or unacceptable toxicity, and subsequently followed off treatment until PSA progression, defined as serum PSA > 0.2 ng/mL. The primary endpoint is PSA progression-free survival (PFS). Secondary endpoints are 36-month PSA PFS rate, metastasis-free survival, time to CRPC, overall survival, and quality of life. Planned accrual is 504 pts, estimated to provide 85% power to detect a hazard ratio of 0.63 in the comparison of PSA PFS between each experimental arm versus the control arm, with an overall two-sided type I error rate of 0.025 for each comparison. The DSMB last reviewed the trial in November 2017 and recommended that the trial continue as planned. Clinical trial information: NCT03009981.