PSMA PET Agent Flotufolastat F 18 Added to NCCN Prostate Cancer Guidelines

Flotufolastat F 18 injection was approved by the FDA in May 2023 to aid in the identification of PSMA-positive prostate cancer lesions.

Injectable prostate-specific membrane antigen (PSMA)–targeted PET imaging agent flotufolastat F 18 (Posluma) has been added to the National Comprehensive Cancer Network (NCCN)’s clinical guidelines for prostate cancer, according to a published update from the NCCN.¹

Flotufolastat F 18 is used in conjunction with PET imaging to identify prostate cancer with potentially metastatic disease in patients who may receive initial definitive therapy, or in those who may have recurrent disease as indicated by an increase in prostate-specific antigen (PSA) level.²

“The NCCN Guidelines are widely used by clinicians and health care providers as a benchmark to assess clinical utility,” Eugene J. Teoh, MBBS, MRCP, FRCR, PhD, chief medical officer at Blue Earth Diagnostics, said in a press release.² “[Flotufolastat F 18] was developed to assist physicians in the detection and localization of prostate cancer. This update recognizes the important ability of PSMA PET imaging procedures to detect and localize newly diagnosed and biochemically recurrent prostate cancer, which are essential to making appropriate patient management decisions.”

Concerning the use of PET imaging for identifying bone metastases in prostate cancer, the guidelines indicate that flotufolastat F 18 should be considered for “equivocal results on initial bone scan” along with sodium fluoride F 18, choline C 11, and fluciclovine F 18 (Axumin). Additionally, the guidelines state that full body imaging with PET/CT or PET/MRI using flotufolastat F 18, Ga-68 PSMA-11, and piflufolastat F 18 (Pylarify) PSMA may be used as an alternative to bone scan.

As of the most recent update, there are several FDA-approved PSMA radiopharmaceuticals that are available for use:

• flotufolastat F 18
• piflufolastat F 18 PSMA
• Ga-68 PSMA-11

The guidelines further elaborate that both flotufolastat F 18 and piflufolastat F 18 PSMA can be used in the same space as Ga-68 PSMA-11, which is used in conjunction with 177–PSMA-617. This is due to evidence supporting these agents’ equivalence in several areas, including PSMA molecular recognition motifs, regular organ biodistribution, and accurate identification of prostate cancer lesions.

Flotufolastat F 18 injection was approved by the FDA in May 2023 to aid in the identification of PSMA-positive prostate cancer lesions.³ The regulatory decision was supported by data from the phase 3 LIGHTHOUSE (NCT04186819) and SPOTLIGHT trials (NCT04186845).^4,5

In the most recent publication of the LIGHTHOUSE trial, investigators administered flotufolastat F 18 to 352 patients with newly diagnosed, unfavorable intermediate- (33%) to very high–risk (67%) prostate cancer.⁶ Approximately 7.8% to 13.0% of patients had flotufolastat F 18–positive pelvic lymph nodes (PLNs) via independent reader, and 24% had at least 1 positive PLN via histopathology.

Investigators reported that the sensitivity rate of PLN identification was 30.0% (95% CI, 19.6%-42.1%) for reader 1, 27.0% (95% CI, 17.2%-39.1%) for reader 2, and 23.0% (95% CI, 13.7%-34.4%) for reader 3, which did not meet the prespecified threshold of 22.5%. The rates for specificity were 93.0% (95% CI, 88.8%-95.9%), 94.0% (95% CI, 89.8%-96.6%), and 97.0% (95% CI, 93.7%-98.7%), respectively.

Investigators concluded that flotufolastat F 18 garnered a high specificity across all risk stratifications.

Additionally, in an update on the phase 3 SPOTLIGHT trial, which included 366 patients with suspected prostate cancer recurrence,⁷ investigators reported that the verified detection rate ranged from 51% (95% CI, 46.1%-56.6%) to 54% (95% CI, 48.8%-59.3%). Moreover, the combined region level positive predictive value across all readers ranged from 46% (95% CI, 42.0%-50.3%) to 60% (95% CI, 55.1%-65.5%). Investigators also reported that the verified detection rate and combined region level positive predictive value in a subgroup of patients with histopathology were above the prespecified thresholds.

The trial’s investigators concluded that flotufolastat F 18 garnered a clinically meaningful verified detection rate in identifying localized recurrent disease.

References

1. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 7.2023. Accessed July 26, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
2. Blue Earth Diagnostics Announces Addition of POSLUMA® (Flotufolastat F 18) Injection to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer. News release. Blue Earth Diagnostics. July 25, 2023. Accessed July 26, 2023. https://bit.ly/3q4IH78
3. U.S. FDA approves Blue Earth Diagnostics’ POSLUMA® (Flotufolastat F 18) injection, first radiohybrid PSMA-targeted PET imaging agent for prostate cancer. News release. Blue Earth Diagnostics. May 30, 2023. Accessed July 26, 2023. https://bit.ly/43baWPD
4. Chapin BF, Koontz BF, LIGHTHOUSE Study Group. Detection of true positive M1 lesions by 18F-rhPSMA-7.3 PET in newly diagnosed prostate cancer: results from the phase 3 prospective LIGHTHOUSE study. J Clin Oncol. 2023;41(suppl 6):315. doi:10.1200/JCO.2023.41.6_suppl.315
5. Lowentritt, B. Impact of Clinical Factors on 18F-rhPSMA-7.3 Detection rates in men with recurrent prostate cancer: findings from the phase 3 SPOTLIGHT study. Presented at 2022 American Society for Radiation Oncology Annual Meeting (ASTRO); October 23-26, 2022; San Antonio, TX. Abstract 1049. doi:10.1016j.ijrobp.2022.07.585
6. Surasi DS, Eiber M, Maurer T, et al. LIGHTHOUSE Study Group. Diagnostic performance and safety of positron emission tomography with 18F-rhPSMA-7.3 in patients with newly diagnosed unfavourable intermediate- to very-high-risk prostate cancer: results from a phase 3, prospective, multicentre study (LIGHTHOUSE). Eur Urol. Published online July 5, 2023. doi:10.1016/j.eururo.2023.06.018
7. Jani AB, Ravizzini GC, Gartrell BA, et al. Diagnostic performance and safety of 18F-rhPSMA-7.3 positron emission tomography in men with suspected prostate cancer recurrence: results from a phase 3, prospective, multicenter study (SPOTLIGHT). J Urol. Published online August 1, 2023. doi:10.1097/JU.0000000000003493