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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)

Publication: Journal of Clinical Oncology

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.

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Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the Alliance Foundation Trials, LLC.

Prior Presentation

Presented in part at the ESMO Annual Meeting, September 9, 2022, Paris, France, the ASCO Genitourinary Cancer Symposium, February 16, 2023, San Francisco, CA, and the AUA Annual Meeting, April 28, 2023, Chicago, IL.

Support

Supported in part by the Alliance Foundation Trials, and in part by funds from Janssen Scientific Affairs, LLC.

Clinical Trial Information

Authors' Disclosures of Potential Conflicts of Interest

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)

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
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Information & Authors

Information

Published In

Journal of Clinical Oncology
PubMed: 38261983

History

Published online: January 23, 2024

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Data Sharing Statement

Deidentified patient data may be requested from Alliance for Clinical Trials in Oncology via [email protected] if data are not publicly available. A formal review process includes verifying the availability of data, conducting a review of any existing agreements that may have implications for the project, and ensuring that any transfer is in compliance with the IRB. The investigator will be required to sign a data release form before transfer.

Authors

Affiliations

University of California, San Francisco, CA
Glenn Heller, PhD
Memorial Sloan Kettering Cancer Center, New York, NY
Mayo Clinic Rochester, Rochester, NY
Memorial Sloan Kettering Cancer Center, New York, NY
Washington University, St. Louis, MO
Mary-Ellen Taplin, MD
Dana-Farber Cancer Institute, Boston, MA
University of Pittsburgh/UPMC, Pittsburgh, PA
Douglas Weckstein, MD
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
Daniel Anderson, MD
HealthPartners, Saint Paul, MN
Baylor College of Medicine, Houston, TX
Alan Tan, MD
Rush University, Chicago, IL
Mayo Clinic Rochester, Rochester, NY
Patrick O'Brien, BS
Mayo Clinic Rochester, Rochester, NY
University of Kansas, Kansas City, KS
Charles J. Ryan, MD
University of Minnesota, Minneapolis, MN
University of Chicago, Chicago, IL
Memorial Sloan Kettering Cancer Center, New York, NY
on behalf of the PRESTO Study Investigators

Notes

Rahul Aggarwal, MD, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, 550 16th St, 6th Floor, Box 3211, San Francisco, CA 94158; e-mail: [email protected].

Author Contributions

Conception and design: Rahul Aggarwal, Mary-Ellen Taplin, James Mohler, Scott Tagawa, Susan Halabi, Patrick O'Brien; Ronald Chen, Charles J. Ryan, Michael J. Morris
Administrative support: Douglas Weckstein, Michael J. Morris
Provision of study materials or patients: Rahul Aggarwal, Han Xiao, Joel Picus, Mary-Ellen Taplin, Leonard Appleman, Douglas Weckstein, James Mohler, Scott Tagawa, Michael J. Morris
Collection and assembly of data: Rahul Aggarwal, David W. Hillman, Han Xiao, Joel Picus, Mary-Ellen Taplin, Tanya Dorff, Leonard Appleman, Douglas Weckstein, Akash Patnaik, Daniel Shevrin, James Mohler, Daniel Anderson, Arpit Rao, Scott Tagawa, Alan Tan, Susan Halabi, Charles J. Ryan, Michael J. Morris
Data analysis and interpretation: Rahul Aggarwal, Glenn Heller, David W. Hillman, Joel Picus, Mary-Ellen Taplin, Tanya Dorff, Leonard Appleman, Douglas Weckstein, Akash Patnaik, Alan Bryce, James Mohler, Arpit Rao, Scott Tagawa, Alan Tan, Susan Halabi, Katharine Dooley, Patrick O'Brien; Ronald Chen, Charles J. Ryan, Scott E. Eggener, Michael J. Morris
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors

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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
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