ASCO GU 2023: Baseline Characteristics Associated with PSA Progression-Free Survival in Patients (Pts) with High-Risk Biochemically Relapsed Prostate Cancer: Results from the Phase 3 PRESTO Study (AFT-19)

( The 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 16th and 18th was host to a prostate cancer poster session. Dr. Rahul Aggarwal presented the results of a secondary analysis of the PRESTO trial evaluating the baseline characteristics associated with progression-free survival in patients with high-risk biochemically relapsed prostate cancer.

The phase III PRESTO trial, that evaluated a 52-week regimen of intensified androgen deprivation therapy with apalutamide +/- abiraterone/prednisone, demonstrated that systermic therapy intensification was associated with prolonged prostate-specific antigen (PSA) progression-free survival (PFS) in patients with high-risk biochemically relapsed prostate cancer. In this secondary analysis of the PRESTO trial, the authors sought to evaluate clinical characteristics associated with PSA PFS in this cohort.

PRESTO is a randomized phase 3, open-label trial of patients with biochemical relapse post- radical prostatectomy, a PSA doubling time (PSADT) of less than or equal to 9 months, and no evidence of distant metastases on conventional imaging (NCT03009981). Patients were randomized 1:1:1 to receive a pre-determined 52-week treatment course of ADT, ADT + apalutamide, or ADT + apalutamide + abiraterone acetate/prednisone, stratified by PSADT (less than 3 versus 3-9 months), with post-treatment follow-up. Evaluable clinical predictors of PSA-PFS included: Gleason score at radical prostatectomy (6 -7, 8, ≥ 9), serum PSA, PSA doubling time at study entry, time interval from radical prostatectomy, and prior receipt of radiation (none, adjuvant, salvage).

This trial included 504 patients (ADT alone: 167, ADT + apalutamide: 168, ADT + apalutamide + abiraterone acetate/prednisone: 169). Baseline patient characteristics were well-balanced between the three arms.

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At the first planned interim analysis, treatment intensification with ADT + apalutamide or ADT + apalutamide + abiraterone was associated with improvements in PSA-PFS:

  • ADT + apalutamide: 24.9 months versus ADT alone: 20.3 months (HR: 0.52, 95% CI: 0.35 to 0.77)
  • ADT + apalutamide + abiraterone acetate/prednisone: 26.0 months versus ADT alone: 20.0 months (HR: 0.48, 95% CI: 0.32 to 0.71)

In the overall cohort, Gleason sum ≥ 9 at diagnosis was associated with a shorter PSA-PFS (log-rank test p-value= 0.041):

  • Gleason Score ≥ 9: Median= 21.9 months
  • Gleason Score 8: Median= 31.1 months
  • Gleason Score 6-7: 25.2 months

Similar results were observed when analysis was restricted to each arm, with a shorter observed median PSA-PFS observed for patients with Gleason ≥ 9 prostate cancer. Serum PSA and PSA doubling time at study entry, time from prior radical prostatectomy, and prior radiation were not significantly associated with PSA-PFS in the overall study cohort or in individual study arms.

In this secondary analysis of the PRESTO trial, the authors concluded that Gleason Score ≥ 9 prostate cancer at diagnosis was associated with shorter time to PSA progression following intensified ADT, administered for 52 weeks in biochemically relapsed prostate cancer. Ongoing analyses from the PRESTO trial will evaluate tissue genetic predictors of adverse oncologic outcomes, including metastasis-free survival.

Presented by: Rahul Aggarwal, MD, Associate Director for Clinical Sciences, UCSF Helen Diller Family Comprehensive Cancer Center; Associate Professor of Hematology/Oncology, University of California in San Francisco, San Francisco, CA

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.