ADT Plus APA With or Without AAP in High-Risk Prostate Cancer

In the PRESTO trial, researchers evaluated whether intensifying androgen deprivation therapy (ADT) increased biochemical progression-free survival (bPFS) in patients with biochemically relapsed prostate cancer (BRPC) and a short prostate-specific antigen doubling time after radical prostatectomy also at high risk for metastases.

The late-breaking data, presented by lead author Rahul Aggarwal at the ESMO Congress 2022, showed that more complete androgen receptor blockade with apalutamide (APA) and abiraterone acetate plus prednisone (AAP) during ADT did prolong bPFS with an acceptable safety profile. Aggarwal added that the study intervention did not negatively affect time to testosterone recovery (TTTR) posttreatment.

This phase 3 trial randomized 504 patients without distant metastases to 52 weeks of treatment with ADT (n=167), ADT and APA (n=168), or ADT, APA, and AAP (n=169). The primary outcome was bPFS, defined as serum PSA more than 0.2 ng/mL after treatment. Additional end points included safety, quality of life (QOL), TTTR, metastasis-free survival (MFS), and time to castration resistance (TTCR).

According to Aggarwal, both of the study’s interventions significantly improved median bPFS versus ADT alone at the first interim analysis:

• 9 months for ADT and APA versus 20.3 months for ADT (hazard ratio [HR], 0.52; 95% CI, 0.35-0.77)
• 0 months for ADT, APA, and AAP versus 20.0 months for ADT (HR, 0.48; 95% CI, 0.32-0.71)

Additionally, median TTTR was 3.9 months for ADT, 3.8 months for ADT and APA, and 4.7 months for ADT, APA, and AAP. The most common grade ≥ 2 adverse event was hypertension (ADT, 19.4%; ADT and APA, 23.4%; ADT, APA, and AAP, 30.4%). A total of 8 patients discontinued treatment due to adverse events.

While the study’s QOL, MFS, and TTCR analyses were not yet complete at the time of the presentation, Aggarwal and colleagues ultimately suggested that “intensification of ADT should be considered in high-risk BRPC.”

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