Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer

The addition of apalutamide to androgen deprivation therapy (ADT) for a finite duration led to a statistically significant prolongation of prostate-specific antigen (PSA) doubling time and biochemical progression-free survival without impacting testosterone recovery time, results from the phase 3 PRESTO trial showed.

Intermittent and continuous ADT are standard approaches for men with biochemically relapsed, non-metastatic prostate cancer after prostatectomy with a short PSA doubling time and a high risk of developing distant metastases and cancer-related mortality [1]. The phase 3 PRESTO trial (NCT03009981) evaluated the efficacy and safety of intensification of ADT for a finite duration on PSA doubling time suppression enabling longer treatment-free intervals within a framework of intermittent treatment. Dr Rahul Aggarwal (University of California San Francisco, CA, USA) presented the first results [2].

In the PRESTO trial, 503 patients (prior radical prostatectomy and radiotherapy, PSA doubling-time < 3 months) were randomised 1:1:1 to receive ADT, ADT plus apalutamide (APA), or ADT plus APA plus abiraterone acetate plus prednisone (AAP) for 52 weeks. The primary endpoint was biochemical progression-free survival (PFS). Secondary endpoints included safety, patient-reported quality-of-life (QoL), time to testosterone recovery (> 50 ng/dL) (TTTR), metastasis-free survival (MFS) and time to castration resistance (TTCR).

Median biochemical PFS was improved in ADT + APA versus ADT alone (20.3 vs 24.9 months; HR 0.52; P= 0.00047). Likewise, median biochemical PFS was improved in ADT + APA + AAP versus ADT alone (20.6 vs 26.0 months; HR 0.48; P=0.00008). Biochemical PFS was independent of PSA doubling time (<3 months, 3–9 months). The addition of APA to ADT did not influence TTTR (3.9 months for ADT vs 3.8 months for ADT + APA), whereas the addition of APA + AAP to ADT led to a slight but not statistically significant prolongation of TTTR (4.8 months for ADT + APA + AAP vs 3.9 months for ADT alone). Grade ≥3 adverse events, in particular hypertension, were increased in the ADT + APA + AAP group.

Based on these results, Dr Aggarwal concluded that “the addition of APA to ADT for a finite duration leads to a statistically significant prolongation of biochemical PFS with no impact on testosterone recovery time. Therefore, this treatment regimen could be considered for high-risk patients with a short PSA doubling time. The addition of AAP to ADT + APA does not appear to further benefit the patient.”

1. Crook JM, et al. N Engl J Med. 2012;367(10):895–903.
2. Aggarwall R, et al. PRESTO: A phase III, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19). Abstract LBA63, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 17 November 202217 May 2024