AFT-19: A Randomized Phase 3 Study in Patients with High Risk Biochemically Relapsed Prostate Cancer

Chicago—There is a high risk for the development of metastatic disease and prostate cancer-related mortality in patients with biochemically relapsed prostate cancer (BRPC) following radical prostatectomy and a short prostate-specific antigen (PSA) doubling time. Intermittent androgen deprivation therapy (ADT) is commonly used in this disease setting but for a majority of patients does not achieve prolonged progression-free survival and treatment-free intervals.

Apalutamide, a next generation androgen receptor antagonist, had efficacy in non-metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate, a prodrug of the CYP17 androgen synthesis inhibitor abiraterone, has prolonged survival in both CRPC and metastatic hormone-sensitive prostate cancer. Researchers, led by Rahul Raj Aggarwal, MD, designed a phase 3 study to test the hypothesis that “the addition of apalutamide with or without abiraterone acetate/prednisone, compared with ADT alone, will prolong disease suppression and potentially eradicate micrometastatic disease with a finite duration of treatment in patients with BRPC.” The study protocol was described in a poster presented at the ASCO 2018 Annual Meeting; the poster was titled A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer: An Alliance Foundation Trial (AFT-19).

The Alliance Foundation trial (AFT-19) is a randomized open-label, three-arm phase 3 study that enrolled its first patient in March 2017. The trial seeks to assess (a) degarelix monotherapy in comparison with each of two experimental arms: (b) degarelix + apalutamide and (c) degarelix + apalutamide + abiraterone acetate/prednisone in patients with BRPC following radical prostatectomy with no metastases on conventional imaging, and a PSA doubling time of ≤9 months.

In the absence of progression or unacceptable toxicity, patients are treated for up to 52 weeks. Post-treatment follow-up continues until PSA progression (defined as serum PSA >02 ng/mL). PSA progression-free survival is the primary end point of interest; secondary end points include 36-month PSA progression-free survival rate, metastasis-free survival, time to CRPC, overall survival, and quality of life.

Planned accrual is 504 patients, the number estimated to provide 85% power to detect a hazard ratio of 0.63 in the comparison of PSA progression-free survival between each experimental arm compared with the control arm. Each comparison will have an overall two-sided type I error rate of 0.025.

The Data and Safety Monitoring Board last reviewed the trial in November 2017 and recommended that the trial continue as planned.

Clinical trial information: NCT03009981.

Source: Aggarwal RR, Eggener SE, Chen RC, et al. A phase 3 study of androgen annihilation in high-risk biochemically relapsed prostate cancer: An Alliance Foundation trial (AFT-19). Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.