The U.S. Food and Drug Administration (FDA) has approved flotufolastat F 18 injection (Posluma, Blue Earth Diagnostics), the first radiohybrid prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agent for men with prostate cancer. This approval marks a significant advancement in the detection and management of prostate cancer, offering improved diagnostic accuracy for metastasis and recurrence.
Clinical Utility and Indications
Posluma is indicated for PET imaging of PSMA-positive lesions in men with prostate cancer who are candidates for initial definitive therapy and those with suspected recurrence based on elevated serum prostate-specific antigen (PSA) levels. The agent binds to and is internalized by PSMA-expressing cells, including prostate cancer cells, which are known to overexpress PSMA. Labeled with fluorine-18 (18F), Posluma allows for high-quality PET imaging of the prostate and other areas of the body where prostate cancer may have spread.
Supporting Clinical Trials: LIGHTHOUSE and SPOTLIGHT
The FDA's decision was supported by data from two phase 3 clinical trials: LIGHTHOUSE (NCT04186819) and SPOTLIGHT (NCT04186845). The LIGHTHOUSE trial focused on patients with newly diagnosed prostate cancer, while the SPOTLIGHT trial evaluated men with suspected prostate cancer recurrence based on elevated PSA levels after previous therapy.
In the LIGHTHOUSE trial, flotufolastat F 18 injection demonstrated high specificity in identifying pelvic lymph nodes compared to histopathology, the standard of truth, in patients with PSMA-positive lesions before radical prostatectomy. The SPOTLIGHT trial showed high detection rates, indicated by positive PET scans, even in patients with low PSA levels. Data presented at the 2023 American Urological Association Annual Meeting showed that in a subset of patients who had received primary treatment and radiation for their disease (n = 76), the overall patient-level detection rate was 99%.
Safety and Adverse Events
Clinical trials reported that Posluma is generally safe and well-tolerated. In the SPOTLIGHT trial, among 391 patients who received the PSMA-targeted PET imaging agent, 4.1% experienced at least one treatment-emergent adverse effect potentially related to the agent. The most common adverse events included hypertension (1.8%), diarrhea (1.0%), injection site reaction (0.5%), and headache (0.5%). No serious adverse reactions were reported.
Expert Commentary
David M. Schuster, MD, a radiologist and nuclear medicine specialist at Emory University School of Medicine and an investigator in the phase 3 trials, noted the unpredictable nature of prostate cancer recurrence, estimating that up to 40% of patients who undergo radical prostatectomy and 50% of those who receive radiation therapy experience recurrence within 10 years. He emphasized that Posluma can serve as a potential decision-making aid in assessing suspected biochemical recurrence of the disease, noting an overall detection rate of 83%.
Commercial Availability
Blue Earth Diagnostics anticipates that Posluma will be commercially available in early June 2023, with availability expanding nationally in the coming months. The agent will be offered through pharmacies connected with manufacturer and distributor PETNet Solutions, a Siemens Healthineers company.
Significance for Prostate Cancer Management
The approval of Posluma represents a significant advancement in prostate cancer imaging, providing physicians with a more accurate and reliable tool for detecting and localizing the disease. This can lead to more informed treatment decisions and improved outcomes for patients with prostate cancer.
