Background
Pts with biochemically relapsed prostate cancer (BRPC) following radical prostatectomy (RP) and a short PSA doubling time (PSADT) are at risk for distant metastases. Apalutamide (APA), an androgen receptor (AR) antagonist, and abiraterone acetate plus prednisone (AAP), prolong survival in the metastatic setting. We evaluated if intensification of androgen deprivation therapy (ADT) prolongs biochemical progression-free survival (bPFS) in BRPC.
Methods
PRESTO is a randomized phase III, open-label trial in pts with BRPC and PSADT ≤ 9 months (mo), without distant metastases on conventional imaging (NCT03009981). Pts were randomized 1:1:1 to receive a finite 52-week treatment course with ADT, ADT + APA, or ADT + APA + AAP, stratified by PSADT (< 3 vs 3–9 mo), with post-treatment follow-up. The primary endpoint of bPFS (serum PSA > 0.2 ng/mL following treatment) was compared for each experimental arm vs. control. Secondary endpoints included safety, patient-reported quality of life (QOL), time to testosterone (T) recovery (> 50 ng/dL) (TTTR), metastasis-free survival (MFS) and time to castration resistance (TTCR).
Results
504 pts were randomized to ADT alone (N = 167), ADT + APA (N = 168) or ADT + APA + AAP (N = 169). At first planned interim analysis, both experimental arms significantly prolonged bPFS compared to the control arm (median 24.9 mo for ADT + APA vs 20.3 mo for ADT, HR = 0.52 (95% CI: 0.35–0.77); median 26.0 mo for ADT + APA + AAP vs 20.0 mo for ADT, HR = 0.48 (95% CI: 0.32–0.71)). Median TTTR was 3.9, 3.8 and 4.7 mo in ADT, ADT + APA, and ADT + APA + AAP arms, respectively. The most common grade ≥ 2 adverse event (AE) was hypertension (19.4%, 23.4%, 30.4% in ADT, ADT + APA and ADT + APA + AAP arms, respectively). Eight pts (1.8%) across all treatment arms stopped treatment for AEs. Follow-up for analysis of QOL, MFS and TTCR is ongoing.
Conclusions
More complete AR blockade with APA in addition to ADT prolongs bPFS with a manageable safety profile, without impacting TTTR following a finite duration of treatment. More hypertension was seen in the AAP-containing treatment arm. Intensification of ADT should be considered in high-risk BRPC. Support: AFT, Janssen; https://acknowledgments.alliancefound.org.
Clinical trial identification
NCT03009981.