Aggarwal et al presented data from PRESTO (AFT-19) at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA63), the first trial to evaluate whether intensifying treatment beyond androgen-deprivation therapy (ADT) by adding apalutamide with or without abiraterone acetate plus prednisone for a finite period would prolong biochemical progression-free survival in patients with high-risk biochemically relapsed prostate cancer.
For patients with rising prostate-specific antigen (PSA), a common treatment approach is to use hormone therapy, also called ADT, to control the spread of cancer. Although ADT is initially effective in lowering PSA, men often relapse and eventually the cancer may become resistant to ADT. The PRESTO/AFT-19 trial showed that combination hormonal therapy, delivered for a finite treatment interval of 12 months, more durably suppresses PSA levels compared to hormone injections alone—without affecting testosterone recovery following the completion of treatment.
“Patients with a fast-rising PSA after prior surgery to treat their prostate cancer are at high risk for the development of distant metastasis,” said the trial’s lead investigator Rahul Aggarwal, MD, of the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center. “Hormone therapy to suppress testosterone levels is a common way to treat this condition, however, treatment can be associated with side effects. We therefore often give hormone therapy for a fixed interval of time, and then stop as part of an intermittent treatment approach.”
PRESTO is a randomized phase III trial that enrolled 504 patients with high-risk biochemically relapsed prostate cancer. Patients in the control arm received ADT alone with intensified treatment adding apalutamide or apalutamide and abiraterone acetate plus prednisone for up to 52 weeks. The primary endpoint of PSA progression-free survival for both apalutamide and apalutamide with abiraterone acetate plus prednisone showed significant improvement over ADT alone (median 24.9 months vs 20.3 months, hazard ratio [HR] = 0.52, 1-sided P-value = .00047; and median 26.0 months vs 20.0 months, HR = 0.48, 1-sided P-value = .00008, respectively). Testosterone recovery was similar across the three treatment arms. Grade 2 or higher adverse effects were similar among arms except for higher hypertension in arm C (with the addition of abiraterone acetate plus prednisone).
These results showed that more complete androgen receptor blockade with apalutamide or apalutamide and abiraterone acetate plus prednisone prolonged disease progression with a manageable side effect profile in patients with high-risk biochemically relapsed prostate cancer compared to ADT alone.
“Longer follow-up is needed to assess the impact of treatment on the risk of developing distant metastasis,” Dr. Aggarwal concluded.
Michael J. Morris, MD
PRESTO was a collaboration between Alliance Foundation Trials and Janssen Pharmaceuticals.
"This trial was a prime example of how industry and academia can partner to move the needle in prostate cancer care,” said Alliance Genitourinary Committee Chair Michael J. Morris, MD, a medical oncologist and Prostate Cancer Section Head at Memorial Sloan Kettering Cancer Center. “The trial was jointly designed and executed and would not have been possible without the expertise and resources of both stakeholders."
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
