Intermittent, Intensified Androgen Deprivation Therapy Provided PSA Survival Benefit for Patients With High-Risk Biochemically Relapsed Prostate Cancer

Interim Analysis From the Phase 3 PRESTO Trial 

For patients with high-risk biochemically relapsed prostate cancer, the addition of apalutamide to androgen deprivation therapy (ADT), with or without the addition of abiraterone acetate and prednisone (AAP), demonstrated a statistically and clinically significant improvement in PSA progression-free survival (PFS) when compared to ADT alone.

According to Rahul Aggarwal, MD, University of California, San Francisco, and coauthors, “the commonly accepted standard of care for patients with high-risk biochemically relapsed prostate cancer” is intermittent ADT, where ADT is “administered for a finite interval followed by periods of surveillance.” Previous studies have shown that “intensification of androgen signaling blockade, via use of next-generation androgen pathway inhibitors, has improved survival outcomes” in both patients with nonmetastatic castration-resistant and metastatic castration-sensitive prostate cancer.

The open-label phase 3 PRESTO trial enrolled 503 patients with biochemically relapsed prostate cancer and a PSA doubling time ≤9 months. Patients were randomized on a 1-to-1-to-1 basis to receive a finite treatment course of ADT (control arm), ADT plus apalutamide, or ADT plus apalutamide and AAP.  The primary end point was PSA-PFS, defined as serum PSA >0.2 ng/mL following the completion of treatment.

In the preplanned interim analysis, both experimental arms significantly prolonged the PSA-PFS when compared with the control arm. In the ADT plus apalutamide arm, the median PSA-PFS was 24.9 months, vs 20.3 months in the control arm (P = .00047). The median PSA-PFS was 26.0 months in the ADT plus apalutamide and AAP vs 20.0 months in the control arm (P = .00008). The median time to testosterone recovery did not differ across the treatment arms. The most common grade ≥3 adverse event was hypertension, occurring in 7.5% of patients in the control arm, 7.4% in the ADT plus apalutamide arm, and 18% in the ADT plus apalutamide and AAP arm.

Dr Aggarwal et al concluded, “Apalutamide plus AST improved PSA-PFS compared with ADT alone without adversely affecting time to testosterone recovery after completion of a finite duration of treatment,” though the further addition of AAP to the regimen did not provide additional benefit to PSA-PFS and was associated with higher toxicity. Study authors added, “these data in aggregate provide support to the potential role for intermittent, intensified ADT in this disease setting.”

Source:

Aggarwal R, Heller G, Xiao H, et al. PRESTO: A phase III, open-label study of intensification of androgen blockade in patients with high-risk biochemically relapsed castration-sensitive prostate cancer (ATF-19). J Clin Oncol. Published on January 23, 2024. doi:10.1200/JCO.23.01157