PRESTO Results Back Intensification of Androgen Blockade in Some High-Risk Patients

By: Celeste L. Dixon
Posted: Tuesday, April 16, 2024

Adding apalutamide, an androgen receptor antagonist, to androgen-deprivation therapy (ADT) should be considered in patients with high-risk biochemically recurrent prostate cancer, according to the results of a 503-patient, randomized, phase III, open-label trial. Rahul Aggarwal, MD, of the University of California, San Francisco, and colleagues reported the outcomes of the PRESTO trial in the Journal of Clinical Oncology.

“The benefit of treatment intensification with respect to PSA progression–free survival was maintained when evaluating the subset of patients who recovered serum testosterone,” they continued. “...These data in aggregate provide support to the potential role for intermittent, intensified ADT in this disease setting.”

All participants (median prostate-specific antigen [PSA] value = 1.8 ng/mL) had undergone radical prostatectomy and had a PSA doubling time of up to 9 months. They were randomly assigned 1:1:1 to receive a 52-week treatment course with ADT (arm 1, control); ADT plus apalutamide (arm 2); or ADT plus apalutamide, abiraterone acetate, and prednisone (arm 3). To evaluate whether intensification of ADT improves outcomes in patients with high-risk biochemically recurrent prostate cancer, who are at risk for distant metastases, “the primary endpoint was PSA progression–free survival, defined as serum PSA > 0.2 ng/mL after treatment completion,” noted the team.

Results at the first planned interim analysis showed that intensified androgen receptor blockade for a finite duration prolonged PSA progression–free survival with a manageable safety profile, and median time to testosterone recovery did not differ across treatment arms. “Both experimental [treatments] significantly prolonged PSA progression–free survival compared with the control arm (median, 24.9 months for arm 2 vs 20.3 months for arm 1, P = .00047; median, 26.0 months for arm 3 vs 20.0 months for arm 1, P = .00008),” Dr. Aggarwal and co-investigators wrote. The most common grade ≥ 3 adverse event was hypertension (7.5%, 7.4%, and 18% in arms 1, 2, and 3, respectively).

Disclosure: For full disclosure of the study authors, visit ascopubs.org.

Journal of Clinical Oncology