The FDA is currently reviewing the results of these trials and is scheduled to make an approval decision by May 28, 2021.
The results of 2 pivotal trials supporting an FDA application for the PSMA PET imaging agent 18F-DCFPyL (Pyl) in prostate cancer have now been published in peer-reviewed academic journals.1
Findings for the 2 trials, the CONDOR study and the OSPREY study, have been published in Clinical Cancer Research2 and the Journal of Urology3, respectively. The FDA is currently reviewing the results of these trials and is scheduled to make an approval decision by May 28, 2021.
“The limitations of conventional imaging modalities for prostate cancer create a need for targeted imaging in the initial assessment of high-risk patients as well as in men with early biochemically relapsed disease,” Michael J. Morris, MD, Prostate Cancer Section Head, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, and lead author of the CONDOR manuscript and senior author on the OSPREY manuscript, stated in a press release.
“The OSPREY trial data highlighted the high positive predictive value, negative predictive value and specificity of PyL in staging high-risk patients. The CONDOR trial demonstrates its high positive predictive value to accurately locate and identify recurrent cancer early and non-invasively. Assuming FDA approval, physicians will be able to use this clinically meaningful information to identify disease, guide treatment plans, and improve disease management,” 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%).
1. Lantheus Announces Publication of PyL™ (18F-DCFPyL) Results from Pivotal Studies. Published online March 2, 2021. Accessed March 2, 2021. https://bwnews.pr/2Ol170g.
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