On May 30, the U.S. Food and Drug Administration (FDA) approved the optimized, high-affinity radiohybrid prostate-specific membrane antigen (PSMA)-targeted positron-emission tomography (PET) imaging agent flotufolastat fluorine-18 (Posluma). Flotufolastat F-18 is indicated for PET imaging of PSMA-positive lesions in patients with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. It is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.
Flotufolastat F-18 is an optimized PSMA-targeted molecule that binds to and is internalized by cells that express PSMA, including prostate cancer cells, which usually overexpress PSMA. It is labeled with the radioisotope fluorine-18 (F-18) to enable PET imaging of the prostate and other areas of the body where prostate cancer may have spread to. The F-18 radioisotope leverages the high image quality of F-18–labeled PSMA PET imaging to facilitate the effective detection of disease and enables broad, readily available geographic access for patients.
LIGHTHOUSE and SPOTLIGHT Trials
The approval of flotufolastat F-18 is based on data from two Blue Earth Diagnostics–sponsored phase III trials—LIGHTHOUSE (ClinicalTrials.gov identifier NCT04186819) and SPOTLIGHT (ClinicalTrials.gov identifier NCT04186845)—designed to establish the safety and diagnostic performance of the agent. Results from the LIGHTHOUSE study demonstrated high specificity for the detection of pelvic lymph nodes as compared to histopathology standard of truth in patients with PSMA-positive lesions prior to radical prostatectomy. The SPOTLIGHT study evaluated flotufolastat F-18 in patients with suspected prostate cancer recurrence based on elevated PSA following prior therapy. Results demonstrated high detection rates (% positive PET scans), even at low PSA levels.
In clinical trials, the safety of flotufolastat F-18 was evaluated in 747 patients with initial or recurrent prostate cancer. The adverse reactions reported in ≥ 0.4% of patients in clinical studies were diarrhea, increase in blood pressure, and injection site pain.
Expert Commentary on the Approval
Brian F. Chapin, MD
David M. Schuster, MD, FACR
“Effective staging in newly diagnosed prostate cancer—determining its presence and helping determine whether it may have metastasized—is critical in establishing optimal clinical management strategies, because up to 25% of patients with primary prostate cancer may have detectable regional pelvic lymph node metastases, which are correlated with a risk for recurrence and associated overall survival,” said Brian F. Chapin, MD, Associate Professor in the Department of Urology, Division of Surgery at The University of Texas MD Anderson Cancer Center, and coordinating investigator of the LIGHTHOUSE study. “Conventional imaging techniques such as [computed tomography] and [magnetic resonance imaging] are limited in the information they may provide. The LIGHTHOUSE study looked at unfavorable intermediate-, high- and very high–risk patients who were scheduled for radical prostatectomy plus pelvic lymph node dissection prior to [flotufolastat F-18] PET. The study showed that [flotufolastat F-18] PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients.”
“The highly variable nature of recurrent prostate cancer presents clinical challenges, and up to 40% of patients who undergo radical prostatectomy and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years,” said David M. Schuster, MD, FACR, Professor of Radiology and Imaging Sciences at Emory University School of Medicine, a researcher at Winship Cancer Institute of Emory University, and coordinating investigator for the SPOTLIGHT study. “The ability to determine the extent and location of recurrent disease is necessary to inform physicians and their patients for appropriate clinical management. The phase III SPOTLIGHT study investigated the diagnostic performance of [flotufolastat F-18] PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease and demonstrated that it offered precision diagnostic performance even at low PSA levels, with an overall 83% detection rate.”
Flotufolastat F-18 will be commercially available in early June 2023, through certain radiopharmacies in the national radiopharmacy network of Blue Earth Diagnostics’ commercial U.S. manufacturer and distributor, PETNET Solutions Inc, A Siemens Healthineers Company. It will become increasingly available nationally in coming months.
