As reported in the Journal of Clinical Oncology by Aggarwal et al, interim analysis of the phase III PRESTO trial showed that the addition of apalutamide as well as the addition of apalutamide plus abiraterone acetate/prednisone (AAP) to androgen-deprivation therapy (ADT) improved prostate-specific antigen (PSA) progression-free survival vs ADT alone in patients with high-risk biochemically relapsed castration-sensitive prostate cancer after radical prostatectomy.
Study Details
In the open-label U.S. multicenter trial, 503 patients with a PSA doubling time of ≤ 9 months were randomly assigned 1:1:1 between March 2017 and April 2022 to receive a 52-week course of either ADT (control group, n = 166), ADT plus apalutamide (n = 168), or ADT plus apalutamide plus AAP (n = 169). Choice and schedule of ADT was at investigator’s discretion; the starting doses of apalutamide, abiraterone acetate, and prednisone were 240 mg once daily, 1,000 mg once daily, and 5 mg once daily, respectively. The primary endpoint was PSA progression-free survival, with PSA progression defined as serum PSA > 0.2 ng/mL after treatment completion.
PSA Progression-Free Survival
At first interim analysis, after a median follow-up of 21.5 months, median PSA progression-free survival was 24.9 months in the ADT/apalutamide group vs 20.3 months in the ADT group (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.35–0.77, P = .00047). At first interim analysis, after a median follow-up of 23.1 months, median PSA progression-free survival was 26.0 months in the ADT plus apalutamide plus AAP group vs 20.0 months in the ADT group (HR = 0.48, 95% CI = 0.32–0.71, P = .00008).
Median time to testosterone recovery did not differ significantly among treatment groups: 3.8 months in the ADT plus apalutamide group vs 3.9 months in the ADT group, and 4.7 months in the ADT plus apalutamide plus AAP group vs 3.9 months in the ADT group.
Adverse Events
Among all patients, the most common adverse events of any grade were hot flashes (78%), fatigue (55%), injection-site reaction (33%), hypertension (31%), insomnia (21%), arthralgias (15%), and hyperglycemia (14%). The most common grade ≥ 3 adverse event was hypertension, observed in 7.5% of patients in the ADT group, 7.4% of the ADT plus apalutamide group, and 18% in the ADT plus apalutamide plus AAP group. Serious adverse events occurred in 8%, 9%, and 17% of patients. Adverse events led to discontinuation of all treatments in 0%, 2%, and 3% of patients. No treatment-related deaths were reported.
The investigators concluded, “Intensified androgen-receptor blockade for a finite duration prolongs PSA progression-free survival with a manageable safety profile, without adversely affecting time to testosterone recovery. The addition of apalutamide to ADT should be considered in patients with high-risk biochemically recurrent prostate cancer.”
Rahul Aggarwal, MD, of the Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Alliance Foundation Trials and by Janssen Scientific Affairs, LLC. For full disclosures of the study authors, visit ascopubs.org.
