FDA approves PSMA PET imaging agent 18F-DCFPyL for prostate cancer

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The FDA has approved the PSMA PET imaging agent 18F-DCFPyL (Pylarify) for identifying suspected metastasis or recurrence of prostate cancer.¹

The approval is based on findings from the CONDOR² and OSPREY³ studies. In the CONDOR study, 63.9% of men with biochemically recurrent prostate cancer who had no evidence of disease on standard-of-care imaging had a change in intended management after their 18F-DCFPyL–PET/CT scan.

“Conventional imaging has significant limitations in detecting prostate cancer, both in initial staging and when the cancer has recurred or spread after initial primary treatment. Specifically, standard imaging poorly detects the early spread to distant organs, such as the lymph nodes, bones, and other organs,” Michael J. Morris, MD, Prostate Cancer Section Head, Genitourinary Medical Oncology, Memorial Sloan Kettering Cancer Center and the lead study investigator in the CONDOR trial and study investigator in the OSPREY trial, said in a press release.

“Pylarify can detect the spread of disease well before standard imaging and can be a transformative diagnostic tool that helps clinicians develop treatment plans based on a much more accurate understanding of a patient’s distribution of disease,” added Morris.

The multicenter phase 3 CONDOR study enrolled men with rising PSA after definitive therapy and negative or equivocal standard-of-care imaging. Patients were required to have a PSA level ≥0.2 if they had undergone radical prostatectomy (RP) or a PSA level ≥2.0 if they were treated with radiation therapy or cryotherapy.

The primary end point was correct localization rate (CLR), defined as percentage of patients with a 1:1 correspondence between at least 1 lesion identified by PyL–PET/CT and the composite standard of truth (pathology, correlative imaging, or PSA response). PyL scans were read by 3 blinded independent central readers.

Overall, there were 208 evaluable patients, about 85% of whom underwent RP, either alone or with radiation. Median PSA level of the cohort was 0.8 ng/mL, and 68.8% had a PSA level <2.0 ng/mL. Some 27.9% had received at least 1 prior systemic therapy.

Detection of disease as manifested by a positive 18F-DCFPyL–PET/CT scan was 65.9%, 59.6%, and 59.1% by the 3 readers.

The prespecified criterion for CLR success was for the lower limit of the 95% CI to exceed 20% for at least 2 of the 3 readers. For every reader, the lower bound of the 95% CI for the CLR was well in excess of the 20% benchmark, meeting the primary end point of the study.

The CLRs were 85.6% (95% CI, 78.8%-92.3%), 87.0% (95% CI, 80.4%-93.6%), and 84.8% (95% CI, 77.8%-91.9%) by the 3 readers. Some 64% of the evaluable patients had a change in intended management due to the scan.

In the phase 2/3 OSPREY trial, PyL was assessed in 2 patients cohorts. Cohort A included men with high-risk, locally advanced prostate cancer, and the researchers assessed the capacity of PyL to detect prostate cancer in pelvic lymph nodes. Cohort B comprised patients with metastatic or recurrent disease and the researchers examined the performance of PyL in detecting distant metastases.

In cohort A, results for PyL in detecting disease in pelvic lymph nodes showed a specificity of 96%-99%, a sensitivity of 31%-42%, and positive predictive value (PPV) of 78%-91%. The sensitivity and PPV rates for detecting metastatic lesions in cohort B were 93%-99% and 81%-88%, respectively.

The OSPREY investigators observed that Pyl was well tolerated. Across all grades, the most common adverse events were dysgeusia (2.6%), headache (1.8%), and fatigue (1.3%).

Reference

1. Lantheus Receives U.S. FDA Approval of PYLARIFY® (piflufolastat F 18) Injection, the First and Only Commercially Available PSMA PET Imaging Agent for Prostate Cancer. Published online May 27, 2021. Accessed May 27, 2021. https://bwnews.pr/3vtMgBh.

2. Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase 3, multicenter study [published online before print February 26, 2021.] doi: 10.1158/1078-0432.CCR-20-4573

3. Pienta KJ, Gorin MA, Rowe SP, et al. 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) [February 26, 2021]. J Urol. doi: 10.1097/JU.0000000000001698