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)
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Published:2024-01-23
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Aggarwal Rahul1ORCID, Heller Glenn2, Hillman David W.3ORCID, Xiao Han2ORCID, Picus Joel4ORCID, Taplin Mary-Ellen5, Dorff Tanya6ORCID, Appleman Leonard7ORCID, Weckstein Douglas8, Patnaik Akash9ORCID, Bryce Alan10ORCID, Shevrin Daniel11ORCID, Mohler James12ORCID, Anderson Daniel13, Rao Arpit14ORCID, Tagawa Scott15ORCID, Tan Alan16, Halabi Susan17ORCID, Dooley Katharine3ORCID, O'Brien Patrick3, Chen Ronald18ORCID, Ryan Charles J.19, Eggener Scott E.9ORCID, Morris Michael J.2ORCID, Aggarwal Rahul, Shevrin Daniel, Tagawa Scott, Kim Charles, Taplin Mary-Ellen, Whang Young, Dakhil Shaker, Smith Raymond, Gartrell Benjamin, Fagbemi Seth, Mowat Rex, Farber Charles, Hashemi Neda, Humeniuk Michael, Ryan Charles, Ellerton John, Olsen Mark, Wang Jennifer, Dorff Tanya, Karina Pascual Sheila, Weckstein Douglas, Weckstein Douglas, Bryce Alan, Mohler James, Michael Randall James, Xiao Han, Patnaik Akash, King David, Picus Joel, Kilari Deepak, Monk Paul, Bitting Rhonda, Appleman Leonard, Eugenio Najera Jose, Rowland Kendrith, Hauke Ralph, Shehadeh Nasfat, Curti Brendan, Gupta Gopal, Tan Alan, Collins Timothy, Beer Tomasz, Tate David, Sheh Bryant, Basnet Alina, Conway James, Gross Howard, Goodman Michael
Affiliation:
1. University of California, San Francisco, CA 2. Memorial Sloan Kettering Cancer Center, New York, NY 3. Mayo Clinic Rochester, Rochester, NY 4. Washington University, St. Louis, MO 5. Dana-Farber Cancer Institute, Boston, MA 6. City of Hope, Duarte, CA 7. University of Pittsburgh/UPMC, Pittsburgh, PA 8. New Hampshire Oncology Hematology, Hooksett, NH 9. University of Chicago, Chicago, IL 10. Mayo Clinic Arizona, Pheonix, AZ 11. NorthShore University HealthSystem, Evanston, IL 12. Roswell Park Cancer Center, Buffalo, NY 13. HealthPartners, Saint Paul, MN 14. Baylor College of Medicine, Houston, TX 15. Weill Cornell, New York, NY 16. Rush University, Chicago, IL 17. Duke University, Durham, NC 18. University of Kansas, Kansas City, KS 19. University of Minnesota, Minneapolis, MN
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.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
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