USE OF THE positron emission tomography (PET) imaging agent piflufolastat F 18 at initial assessment in men with high-risk prostate cancer may have a substantial impact on staging and management decisions, according to data presented at the 2021 annual meeting of the American Urological Association (AUA2021) by Peter R. Carroll, MD, MPH, Professor and Chair of the Department of Urology at the University of California San Francisco (UCSF).1
Piflufolastat F 18 (formerly referred to as 18F-DCFPyL or PyL) targets prostate-specific membrane antigen (PSMA), a protein that is overexpressed in >90% of primary and metastatic prostate cancer cells. Binding to this target allows detection by PET of recurrent and/or metastatic prostate cancer. Piflufolastat F 18 is administered as a bolus intravenous injection and was approved by the US Food and Drug Administration (FDA) in May 2021 for use in men with prostate cancer and suspected metastasis or recurrence.2
The data on piflufolastat F 18 presented at AUA2021 came from OSPREY, a prospective, multicenter, open-label Phase 2/3 trial that formed part of the basis for its regulatory approval.3 The OSPREY trial evaluated the safety and diagnostic performance of piflufolastat F 18 Injection in patients with at least high-risk prostate cancer who were planned for radical prostatectomy with pelvic lymphadenectomy (Cohort A, 268 patients) or in patients with radiological evidence of locally recurrent or metastatic disease considered viable for biopsy (Cohort B, 117 patients). The OSPREY study was supported by funding from Progenics Pharmaceuticals, Inc, a subsidiary of Lantheus Holdings (North Billerica, MA) which markets piflufolastat F 18 in the US.
Dr. Carroll reported on a study in Cohort A patients, the goal of which was to evaluate the diagnostic performance of piflufolastat F 18 PET/CT using a histopathology truth standard, compared with conventional imaging. Piflufolastat F 18 was administered a single dose of 9 mCi, followed by PET/CT acquisition 1-2 hours later. Three blinded, independent central readers evaluated the piflufolastat F 18 PET/CT scans and imaging results were compared with surgical pathology as the truth standard. Changes to clinical management plans were evaluated based on review of individual patient-level baseline clinical and conventional imaging data assessed by an independent central panel of experts using Medical Management Questionnaires completed before and after piflufolastat F 18 PET/CT.
Compared with conventional imaging, piflufolastat F 18 PET/CT was associated with significant changes in staging, identifying occult N1 and M1 disease in 19% and 12.3%, respectively, of high-risk patients scheduled to undergo radical prostatectomy with pelvic lymphadenectomy. Piflufolastat F 18 PET/CT led to substantial changes in planned management, with 43.6% of patients (115/264) having changes in planned management as a result of piflufolastat F 18 imaging. Change was seen in all groups: a change in surgery or type of surgery was recommended in 39.9% of patients, a change in radiation therapy in 25.8%, and a change in planned hormonal or androgen deprivation therapy (ADT) in 43.6%, a “substantial” difference, Dr. Carroll noted. “Changes went both ways,” he added. In patients in whom surgery was planned, 25.2% were switched from “Yes” to “No” and 74.8% from “No” to “Yes.” In radiation therapy planning, changes were 72.1% “Yes” to “No” and 27.9% “No” to “Yes,”. and in planned hormonal therapy, 67.0% “Yes” to “No” and 22.6% “No” to “Yes.”
Piflufolastat F 18 PET/CT was seen to be safe, with only 2% of patients developing mild side effects like headaches and fatigue, Dr. Carroll added.
“The key question for all PSMA-based trials will be, even though we have done substantial change in management, does the change in management alter long-term outcome?” Dr. Carroll asked. This is currently being addressed in clinical trials, he noted. “It’s my hypothesis that, in fact, change in management does have favorable impact on long-term outcomes. I think for me, the only question is, what is the magnitude of the benefit?” he declared. “We will have to follow such patients, to determine whether or not it has an impact overall on outcomes, including development of metastatic disease, overall survival, and prostate cancer specific survival.”
- Carroll P, Stephan Probst, Steven P. Rowe, et al. Changes to initial risk assessment and intended patient management in high-risk prostate cancer: an exploratory analysis of cohort A from the OSPREY trial. . J Urol. 2021;26(3S, suppl):e181-e182. Abstract MP11-11. DOI: 10.1097/JU.0000000000001984.11
- FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. News release, US Food & Drug Administration (FDA), May 27, 2021. https://www.fda.gov/ drugs/drug-safety-and-availability/fda-approves-second-psma-targeted-pet-imaging- drug-men-prostate-cancer
- Pienta KJ, Gorin MA, Rowe SP, et al; OSPREY Study Group. A Phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/ CT with 18F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206(1):52-61. DOI: 10.1097/JU.0000000000001698