A Phase II, Open-Label Study to Assess Safety and Management Change Using <sup>68</sup>Ga-THP PSMA PET/CT in Patients with High-Risk Primary Prostate Cancer or Biochemical Recurrence After Radical Treatment: The PRONOUNCED Study
Asim Afaq, Heather Payne, Reena Davda, John Hines, Gary Cook, Marie Meagher, Dimitrios Priftakis, Victoria Warbey, Anand Kelkar, Clément Orczyk, Anita Mitra, Sarah Needleman, Michael J. Ferris, G.E.D. Mullen, Jamshed Bomanji
Abstract
Our objectives were to assess the safety and clinical impact of a novel, kit-based formulation of 68 Ga-tris(hydroxypyridinone) ( 68 Ga-THP) prostate-specific membrane antigen (PSMA) for PET/ CT in guiding the management of patients with prostate cancer. Methods: Patients were prospectively recruited to group A (highrisk untreated prostate cancer; Gleason score $ 4 1 3, or prostate-specific antigen (PSA) level . 20 ng/mL or clinical stage . T2c), group B (biochemical recurrence and eligible for salvage treatment after radical prostatectomy with 2 consecutive rises in PSA with a 3-mo interval between reads and a final PSA level . 0.1 ng/mL or a PSA level $ 0.5 ng/mL), or group C (biochemical recurrence with radical curative radiotherapy or brachytherapy at least 3 mo before enrollment, and an increase in PSA level . 2.0 ng/mL above the nadir level after radiotherapy or brachytherapy). Patients underwent evaluation with PET/CT 60 min after intravenous administration of 160 6 30 MBq of 68 Ga-THP PSMA. Safety was assessed through vital signs, cardiovascular profile, serum hematology, biochemistry, urinalysis, PSA, and adverse events (AEs). A change in management was reported when the predefined clinical management of the patient was altered as a result of the 68 Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT: 20 in group A, 21 in group B, and 8 in group C. No patients experienced serious AEs, discontinued the study because of AEs, or died during the study. Two patients had treatment-emergent AEs attributed to 68 Ga-THP PSMA (pruritus in one patient and a rash at the intravenous catheter site in another). A management change secondary to the PET/CT findings occurred in 42.9% of all patients: 30% in group A, 42.9% in group B, and 75% in group C. Conclusion: 68 Ga-THP PSMA was safe to use, with no serious AEs and no AEs resulting in withdrawal from the study. 68 Ga-THP PSMA PET/CT changed the management of 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned phase III study of 68 Ga-THP PSMA in patients with prostate cancer.