FDA approves flotufolastat F 18 for PSMA-PET imaging in prostate cancer

The FDA has approved flotufolastat F 18 (formerly ¹⁸F-rhPSMA-7.3; trade name, Posluma) for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum PSA level.¹

The approval of flotufolastat F 18 is based on findings from the phase 3 SPOTLIGHT and LIGHTHOUSE trials. Flotufolastat F 18 will be commercially available in June 2023.

SPOTLIGHT data

The latest data from the phase 3 SPOTLIGHT trial were presented at the 2022 AUA Annual Meeting and showed that compared with baseline conventional imaging, PET imaging with ¹⁸F-rhPSMA-7.3 frequently led to post-scan disease upstaging in men with prostate cancer recurrence.²

“The phase 3 SPOTLIGHT study investigated the diagnostic performance of Posluma 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,” said David M. Schuster, MD,

Among 250 of 366 men in the efficacy analysis population who had negative baseline conventional imaging, ¹⁸F-rhPSMA-7.3 showed a correct detection rate between 45% and 47%, which is the percentage of patients scanned with at least one true positive PET finding compared with the Standard of Truth of histopathology or confirmatory conventional imaging. Notably, upstaging results were found to vary based on prior treatment and anatomical region.

Initial data from SPOTLIGHT (NCT04186845) previously presented at the 2022 Genitourinary Cancers Symposium showed that the overall detection rate in patients who had an evaluable ¹⁸F-rhPSMA-7.3 scan was 83% by majority read.³

SPOTLIGHT enrolled male patients who were at least 18 years of age and received prior curative intent treatment for localized prostate cancer. Patients were required to have elevated PSA that could indicate biochemical recurrence and be eligible for salvage therapy.

¹⁸F-rhPSMA-7.3 was administered at a dose of 296 MBq/8 mCi, and PET/CT scans were given between 50 and 70 minutes following injection. Scans were then evaluated by 3 blinded central readers. The Standard of Truth was histopathology or confirmatory conventional imaging. Biopsies took place with 60 days following PET scans, and confirmatory imaging was conducted within 90 days.

Of the 420 patients who consented for the trial, 391 received ¹⁸F-rhPSMA-7.3, of which 389 underwent an evaluable PET/CT scan. Furthermore, 366 patients had sufficient data to determine Standard of Truth; these patients comprised the efficacy-evaluable population. Specifically, 69 patients had Standard of Truth determined by histopathology compared with imaging in 297 patients.

In this population, the mean age was 68.4 years (range, 43-85). The median PSA was 1.27 ng/mL (range, 0.03-134.6), and most patients had a Gleason grade group of 3 (30%).

Additional data showed the ¹⁸F-rhPSMA-7.3 detection rate was 88% compared with a correct detection rate of 57%.

In patients with negative baseline conventional imaging in the prostate bed region, between 3.5% and 8.0% of patients post prostatectomy showed true positive detections compared with between 39% and 41% of patients post radiation therapy.

In patients with negative baseline conventional imaging in the pelvic lymph node region, between 18% and 21% of patients post prostatectomy showed true positive detections vs 6.5% of patients post radiation. In patients with negative baseline conventional imaging in the extra-pelvic region, between 21% and 26% of patients post prostatectomy showed true positive detections vs between 20% and 30% of patients post radiation.

“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,” David M. Schuster, MD, FACR, Emory University School of Medicine, 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 phase 3 SPOTLIGHT study, stated in a press release.1

“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 3 SPOTLIGHT study investigated the diagnostic performance of Posluma 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,” added Schuster.

LIGHTHOUSE data

Initial data from the phase 3 LIGHTHOUSE trial presented at the 2022 SUO Annual Meeting showed that use of ¹⁸F-rHPSMA-7.3 PET prior to prostatectomy was associated with positive disease detection and also provided clinically important information.⁴

Of the 296 patients included in the efficacy population, 7.8% to 13.0% had a ¹⁸F-rHPSMA-7.3 PET–positive pelvic lymph node according to 3 readers. Moreover, extrapelvic lesions were identified in 16% to 28% of patients in an extended population that included those who received ¹⁸F-rHPSMA-7.3 PET regardless of surgery (n = 352).

The study included patients with unfavorable-risk, high-risk, or very high–risk newly diagnosed disease set to undergo radical prostatectomy with regional pelvic lymph node dissection. PET/CT was performed 50 to 70 minutes following a 296 MBq (8mCi) intravenous dose of ¹⁸F-rHPSMA-7.3.

The images were interpreted by local readers prior to surgery and were subsequently sent for blinded independent evaluation by 3 central readers. Moreover, histopathology was performed with 30 days after PET.

The trial’s co-primary end points were patient level sensitivity and specificity in terms of detecting pelvic lymph node metastases. The prespecified threshold for sensitivity and specificity were 22.5% and 82.5%, respectively. The efficacy analysis population included patients who received ¹⁸F-rHPSMA-7.3 PET followed by surgery.

The trial did not meet the prespecified statistical threshold for sensitivity, which ranged between 23% to 30%. Investigators noted that sensitivity was higher for those with high-risk or very high–risk disease vs unfavorable intermediate-risk disease.

Moreover, specificity was between 93% to 97% and exceeded the threshold across all readers. Specificity was also high across all readers for both disease risk stratifications, measuring 93% or higher.

“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,” Brian F. Chapin, MD, associate professor, Department Of Urology, Division Of Surgery, The University of Texas MD Anderson Cancer Center, and coordinating investigator of the Phase 3 LIGHTHOUSE study, stated in a press release.

“Conventional imaging techniques such as CT and MRI 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 Posluma PET. The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients.”

Safety

The safety of flotufolastat F 18 was evaluated in a population of 747 patients with initial or recurrent prostate cancer enrolled across clinical trials. The most common (≥0.4% incidence) adverse reactions in the studies were diarrhea, blood pressure increase, and injection site pain.

References

1. U.S. FDA Approves Blue Earth Diagnostics’ POSLUMA® (Flotufolastat F 18) Injection, First Radiohybrid PSMA-targeted PET Imaging Agent for Prostate Cancer. Accessed May 30, 2023. https://tinyurl.com/mpbdk5br

2. Fleming MT. Impact of 18F-rhPSMA-7.3 PET on upstaging of patients with prostate cancer recurrence: results from the prospective, phase 3, multicenter, SPOTLIGHT study. Presented at: 2022 AUA Annual Meeting; May 13-16, 2022; New Orleans, LA. Abstract PLLBA-02.

3. Schuster DM. Detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence: results from a phase 3, prospective, multicenter study (SPOTLIGHT). J Clin Oncol. 2022(suppl 6):9. doi:10.1200/JCO.2022.40.6_suppl.009

4. Chapin BF. Diagnostic performance and safety of 18F-rhPSMA-7.3 PET in patients with newly diagnosed prostate cancer: results from a phase 3, prospective, multicenter study (LIGHTHOUSE). Poster presented at Society for Urologic Oncology (SUO) 23rd Annual Meeting; November 30-December 2, 2022; San Diego, CA. Poster 134.