Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide, an androgen receptor antagonist, and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. We evaluated whether intensification of androgen-deprivation therapy (ADT) improves outcomes in BRPC.
PRESTO is a randomized phase III, open-label trial in patients with BRPC and PSA doubling time ≤9 months (ClinicalTrials.gov identifier: NCT03009981). Patients were randomly assigned 1:1:1 to receive a finite 52-week treatment course with ADT control, ADT + apalutamide, or ADT + apalutamide + AAP. The primary end point was PSA progression-free survival (PSA-PFS), defined as serum PSA >0.2 ng/mL after treatment completion.
Five hundred three patients were enrolled. The median PSA was 1.8 ng/mL (IQR, 1.0-3.6). At the first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with the control arm (median, 24.9 months for ADT + apalutamide v 20.3 months for ADT; hazard ratio [HR], 0.52 [95% CI, 0.35 to 0.77]; P = .00047; median, 26.0 months for ADT + apalutamide + AAP v 20.0 months for ADT; HR, 0.48 [95% CI, 0.32 to 0.71]; P = .00008). Median time to testosterone recovery did not differ across treatment arms. The most common grade ≥3 adverse event was hypertension (7.5%, 7.4%, and 18% in ADT, ADT + apalutamide, and ADT + apalutamide + AAP arms, respectively).
Intensified AR blockade for a finite duration prolongs PSA-PFS with a manageable safety profile, without adversely affecting time to testosterone recovery. The addition of apalutamide to ADT should be considered in patients with high-risk BRPC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Jan 23 [Epub ahead of print]
Rahul Aggarwal, Glenn Heller, David W Hillman, Han Xiao, Joel Picus, Mary-Ellen Taplin, Tanya Dorff, Leonard Appleman, Douglas Weckstein, Akash Patnaik, Alan Bryce, Daniel Shevrin, James Mohler, Daniel Anderson, Arpit Rao, Scott Tagawa, Alan Tan, Susan Halabi, Katharine Dooley, Patrick O'Brien, Ronald Chen, Charles J Ryan, Scott E Eggener, Michael J Morris, EORTC-55994 Study Group
University of California, San Francisco, CA., Memorial Sloan Kettering Cancer Center, New York, NY., Mayo Clinic Rochester, Rochester, NY., Washington University, St. Louis, MO., Dana-Farber Cancer Institute, Boston, MA., City of Hope, Duarte, CA., University of Pittsburgh/UPMC, Pittsburgh, PA., New Hampshire Oncology Hematology, Hooksett, NH., University of Chicago, Chicago, IL., Mayo Clinic Arizona, Pheonix, AZ., NorthShore University HealthSystem, Evanston, IL., Roswell Park Cancer Center, Buffalo, NY., HealthPartners, Saint Paul, MN., Baylor College of Medicine, Houston, TX., Weill Cornell, New York, NY., Rush University, Chicago, IL., Duke University, Durham, NC., University of Kansas, Kansas City, KS., University of Minnesota, Minneapolis, MN.