Adding apalutamide to androgen deprivation therapy (ADT) prolongs prostate-specific antigen (PSA) progression-free survival (PFS) in patients with biochemically recurrent prostate cancer, according to results from the phase 3 PRESTO trial.

The results also suggest that adding abiraterone acetate, prednisone, and apalutamide to ADT prolongs PSA PFS. However, it isn’t clear if this 4-drug combination provides an additional benefit over the 2-drug combination, as the trial was not powered to compare these 2 interventions.

These findings were presented at ESMO Congress 2022 by Rahul Aggarwal, MD, of the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

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The PRESTO study ( Identifier: NCT03009981) enrolled 503 patients who had undergone radical prostatectomy and had biochemical recurrence with PSA levels greater than 0.5 ng/mL and a doubling time of 9 months or less. Patients had no metastases on conventional imaging, and their last dose of ADT was more than 9 months prior to study entry.

At baseline, the patients had a median age of 66.7 years, and 83.7% were White. The median PSA level was 1.77 ng/mL, and 74.2% of patients had a PSA doubling time of 3-9 months.

The patients were randomly assigned to receive 1 of the following treatments for 52 weeks or until disease progression:

  • Luteinizing hormone-releasing hormone (LHRH) analog monotherapy (n=166)
  • LHRH analog plus apalutamide (n=168)
  • LHRH analog, apalutamide, abiraterone acetate, and prednisone (n=169).

Results showed that apalutamide improved PSA PFS. At a median follow-up of 21.5 months, the median PSA PFS was 20.3 months in the ADT monotherapy arm and 24.9 months in the apalutamide-ADT arm (hazard ratio [HR], 0.52; 95% CI, 0.35-0.77; P =.00047).

Likewise, adding apalutamide, abiraterone acetate, and prednisone to ADT prolonged PSA PFS. At a median follow-up of 21.3 months, the median PSA PFS was 20.0 months in the ADT monotherapy arm and 26.0 months in the 4-drug arm (HR, 0.48; 95% CI, 0.32-0.71; P =.00008).

A subgroup analysis showed a benefit with both experimental arms in patients with a PSA doubling time less than 3 months and in those with a PSA doubling time of 3-9 months.

In the testosterone-evaluable population, prolonged PSA PFS was observed in the apalutamide-ADT arm (HR, 0.53; 95% CI, 0.34-0.82; P =.00197) and the 4-drug arm (HR, 0.60; 95% CI, 0.39-0.92; P =.00851) compared with the ADT-alone arm. There were no significant differences between the arms in time to testosterone recovery (>50 ng/dL).

Adverse events (AEs) occurred in 90.6% of patients in the monotherapy arm, 90.8% in the 2-drug arm, and 96.3% in the 4-drug arm. Grade 3-4 AEs occurred in 18.8%, 25.2%, and 37.9%, respectively.

The most common grade 3 or higher AE was hypertension, which occurred in 8% of the monotherapy recipients, 7% of the dual therapy recipients, and 19% of patients who received the 4-drug combination.

Follow-up for this trial is ongoing, and the researchers aim to determine the impact of ADT plus androgen receptor pathway inhibition on patient-reported outcomes, time to castration resistance, and metastasis-free survival.

However, Dr Aggarwal noted that treatment decisions in biochemically recurrent prostate cancer are often predicated on PSA kinetics alone. Therefore, ADT plus apalutamide could be considered for high-risk patients with a short PSA doubling time.

Disclosures: This research was supported by Alliance Foundation Trials, LLC, and Janssen Research & Development, LLC. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.


Aggarwal R, Heller G, Hillman D, et al. PRESTO: A phase 3, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19). Presented at ESMO 2022; September 9-13, 2022. Abstract LBA63.