18F-DCFPyL, PET imaging agent of prostate-specific membrane (PSMA) was detected, detected and locally detected metastatic lesions with high localized accuracy (CLR) and positive predictive value (PPV), according to data from the stage 3 test important CONDOR (PPV) (NCT03739684) presented at the 2021 Genitourinary Cancer Symposium.1
The FDA is currently preparing to decide on a new drug (NDA) application for the PSMA PET imaging manufacturer.2
The multicenter phase 3 study showed CONDOR (NCT03739684) men with prostate-specific antigen (PSA) elevation after definitive treatment and normal or negative images of routine care. Patients were required to have a PSA level of 0.2 or higher if they had undergone radical prostatectomy (RP) or a PSA level of 2.0 or higher if treated with radiation therapy or cryotherapy.
The small radiolabeled molecule 18F-DCFPyL targets the extracellular domain of PSMA. Imaging is expected to begin 1 to 2 hours after intravenous administration of 18F-DCFPyL as bolus injection.
The key endpoint of the study was CLR, defined as the percentage of patients with 1: 1 contact between at least 1 lesion marked with Peel – PET / CT and the complex rate of fact (SOT; N = 132: pathology, correlation imaging, or PSA response). Skin scans were read by 3 blind medium independent readers. The primary secondary endpoint was the percentage of patients in whom 18F-DCFPyL PET / CT underwent a change in the intended treatment.
In total, 208 patients were assessed, with approximately 85% under RP, alone or by radiation. The median PSA level of the group was 0.8 ng / mL, and the PSA rate was 68.8% lower than 2.0 ng / mL. Some 27.9% had received at least 1 prior systemic treatment. Disease as revealed by advanced scan 18F-DCFPyL – PET / CT was detected at 65.9%, 59.6%, and 59.1% by all 3 readers.
The prescribed criterion for CLR success was that the lower limit of 95% CI would be higher than 20% for at least 2 of the 3 readers. For all readers, the minimum 95% CI for the CLR was well above the 20% criterion, meeting the main endpoint 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%) with the 3 readers.
PPV was also high, with a range of 88.7% to 90.7% across all 3 readers. Further, the high CLR and PPV were maintained across the 3 segments of SOT. For histopathology (n = 31) the CLR domains ranged from 78.6 to 82.8% and the PPV domains were 92.9% to 93.3%. For correlated images (n = 100) the ranges were 86.1% to 88.6% and 87.% to 89.5%, respectively. The ranges were 100% for PSA response.
“Detected PSF-targeted 18F-DCFPyL-PET / CT and local metastatic lesions with high CLR and PPV regardless of the criterion explaining CLR used, in men with BCR who had baseline imaging negative or equivalent line, ”said first study author Frederic Pouliot, MD, PhD, assistant professor, Department of Surgery, Faculty of Medical Sciences, Université Lavaland, Quebec, Canada, and coauthors.
Regarding the secondary endpoint of treatment change, as measured through pre- and post-PET questionnaires, 63.9% of assessed patients had a change in control in effect due to 18F-DCFPyL-PET / CT. Of these changes, 78.6% were induced by 18F-DCFPyL-PET / CT positive results and 21.4% were induced by negative results.
The changes involved 58 patients transitioning from saving local treatment to systemic treatment, 49 patients switching from observation to starting treatment, 43 patients switching from non-medical systemic treatment to saving local treatment, with 9 patients scaling back from planned treatment to observation.
The NDA for 18F-DCFPyL-PET / CT under consideration by the FDA also includes supporting data from the OSPREY phase 2/3 test, in which 18F-DCFPyL-PET / CT was evaluated the 2 patient consortium.2 Cohort A included men with high-risk, locally advanced prostate cancer, and the researchers evaluated the ability of 18F-DCFPyL-PET / CT to detect prostate cancer in pelvic lymph nodes. Cohort B included patients with metastatic or recurrent metastases and the researchers examined the performance of 18F-DCFPyL-PET / CT in detecting distant metastases.
In cohort A, results for 18F-DCFPyL-PET / CT in detection of infection in pelvic lymph nodes showed a specificity of 96% to 99%, a sensitivity of 31% to 42%, and a PPV of 78% to 91%. Sensitivity and PPV levels for the detection of metastatic lesions in cohort B ranged from 93% to 99% and 81% to 88%, respectively.
References
- Pouliot F, Gorin MA, Rowe SP, et al. PSMA-focused image with 18F-DCFPyL-PET / CT in patients (pts) with biochemical recurrent prostate cancer (PCa): A phase III study (CONDOR) —A subanalysis of the correct localization rate (CLR) and value before progressive index (PPV) by fact level. J Clin Oncol. 2021; 39 (solair 6): 33. doi: 10.1200 / JCO.2021.39.6_suppl.33
- The PDUFA implementation date of May 28, 2021 has been set by the U.S. Food and Drug Administration. Published online December 9, 2020. https://bit.ly/2KtYerG. Accessed February 13, 2021