Radiographic Progression-Free Survival in CAPItello-281

Clinical trials targeting molecularly defined populations are redefining therapeutic expectations in metastatic prostate cancer. Gordon A. Brown, DO, FACOS, an associate professor at Rowan University School of Osteopathic Medicine, program director of Urologic Surgery at Rowan University School of Osteopathic Medicine, and director of New Jersey Urology’s Center for Advanced Therapeutics, discusses findings from the phase 3 CAPItello-281 trial (NCT04493853), in which the addition of the AKT inhibitor capivasertib to abiraterone and ADT significantly improved radiographic progression-free survival (rPFS) in patients with PTEN-deficient mHSPC. The study demonstrated a 7.5-month improvement in median rPFS compared with standard therapy alone.

Brown emphasizes that this benefit is particularly meaningful because the comparator arm represented an established standard of care rather than inactive therapy. The results therefore reflect true treatment intensification in a biologically high-risk population. Importantly, radiographic progression frequently occurred without prostate-specific antigen progression, highlighting limitations of PSA-based monitoring in PTEN-deficient disease.

The observed HR of 0.81 indicates an approximately 20% reduction in risk of progression or death, with early and sustained separation of treatment curves. Brown notes that these findings support early biomarker identification and intervention, suggesting that targeting AKT signaling may meaningfully delay disease progression when incorporated upfront in appropriately selected patients.