Faculty Collaboration Database

PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol 2024 Apr 01;42(10):1114-1123

Date

01/23/2024

Pubmed ID

38261983

DOI

10.1200/JCO.23.01157

Scopus ID

2-s2.0-85186714362 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.

Author List

Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ, EORTC-55994 Study Group

Author

Deepak Kilari MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Abiraterone Acetate
Androgen Antagonists
Androgens
Castration
Humans
Male
Prednisone
Prostate-Specific Antigen
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Testosterone