[ad_1]
18F-DCFPyL, an experimental prostate-specific membrane antigen (PSMA) PET imaging agent detects and localizes metastatic lesions with a high correct localization rate (CLR) and positive predictive value (PPV), according to data from the Pivotal phase 3 CONDOR trial (NCT03739684) presented at the 2021 Symposium on genitourinary cancers.1
Currently, the FDA is preparing to make a decision on a New Drug Application (NDA) for the imaging agent PSMA PET.2
The multicenter phase 3 CONDOR study (NCT03739684) enrolled men with elevated prostate specific antigen (PSA) after definitive treatment and negative or equivocal standard of care imaging. 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 they were treated with radiotherapy or cryotherapy.
The radiolabeled 18F-DCFPyL small molecule targets the extracellular domain of PSMA. Imaging is supposed to start 1 to 2 hours after the intravenous administration of 18F-DCFPyL as a bolus.
The primary endpoint of the study was the CLR, defined as the percentage of patients with a 1: 1 match between at least 1 lesion identified by Peel – PET / CT and the composite standard of truth (SOT; N = 132 : pathology, correlative imaging or PSA response). The Peel scans were read by 3 independent central readers blind. The main secondary endpoint was the percentage of patients in whom PET / CT 18F-DCFPyL led to a change in planned therapy.
Overall, there were 208 evaluable patients, of whom approximately 85% underwent RP, alone or with radiation therapy. The median PSA level of the cohort was 0.8 ng / ml and 68.8% had a PSA level below 2.0 ng / ml. Some 27.9% had received at least one previous systemic treatment. The detection of disease manifested by a positive 18F-DCFPyL – PET / CT scanner was 65.9%, 59.6% and 59.1% by the 3 readers.
The pre-specified criterion for the success of the CLR was that the lower limit of the 95% CI exceeds 20% for at least 2 of the 3 readers. For each reader, the lower limit of the 95% CI for the CLR was well above the 20% benchmark, meeting the primary 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% (CI 95%, 77.8% -91.9%) by the 3 readers.
PPV was also high, with a range of 88.7% to 90.7% for the 3 readers. Additionally, the high CLR and PPV were maintained in all 3 SOT categories. For histopathology (n = 31), the CLR ranges were 78.6 to 82.8% and the PPV ranges were 92.9% to 93.3%. For correlative imaging (n = 100), the ranges were 86.1% to 88.6% and 87% to 89.5%, respectively. The ranges were both 100% for the PSA response.
“PSMA-targeted 18F-DCFPyL-CT / CT metastatic lesions detected and localized metastatic lesions with an elevated CLR and PPV, regardless of the criteria defined by the CLR that was used, in men with BCR who had negative or equivocal baseline standard imagery, ”study first author Frédéric Pouliot, MD, PhD, Assistant Professor, Department of Surgery, Faculty of Medicine, Lavaland University, Quebec, Canada, and co-authors wrote.
Regarding the secondary endpoint of treatment change, as measured by the pre- and post-PET questionnaires, 63.9% of evaluable patients experienced a change in planned management due to 18F-DCFPyL- PET / CT. Of these changes, 78.6% were triggered by positive results for 18F-DCFPyL-PET / CT and 21.4% were caused by negative results.
The changes included 58 patients switching from local rescue therapy to systemic therapy, 49 patients switching from observation to initial therapy, 43 patients switching from non-curative systemic therapy to local rescue therapy and 9 patients switching from planned treatment to observation.
The FDA’s proposed NDA for 18F-DCFPyL-PET / CT also includes supporting data from the OSPREY Phase 2/3 trial, in which 18F-DCFPyL-PET / CT was evaluated in 2 patient cohorts.2 Cohort A included men with high-risk, locally advanced prostate cancer, and the researchers assessed the ability of 18F-DCFPyL-PET / CT to detect prostate cancer in pelvic lymph nodes. Cohort B included patients with metastatic or recurrent disease and the researchers examined the performance of 18F-DCFPyL-PET / CT in detecting distant metastases.
In Cohort A, the results of 18F-DCFPyL-PET / CT in detecting disease in pelvic lymph nodes showed specificity of 96% to 99%, sensitivity of 31% to 42% and PPV of 78 % to 91%. The sensitivity and PPV rates for the detection of metastatic lesions in cohort B were 93% to 99% and 81% to 88%, respectively.
The references
- Pouliot F, Gorin MA, Rowe SP, et al. PSMA-targeted imaging with 18F-DCFPyL-PET / CT in patients (pts) with biochemically recurrent prostate cancer (PCa): A phase III study (CONDOR) – A sub-analysis of the rate of correct localization (CLR) and positive predictive value (PPV) per standard of truth. J Clin Oncol. 2021; 39 (suppl 6): 33. doi: 10.1200 / JCO.2021.39.6_suppl.33
- PDUFA action date of May 28, 2021 assigned by the US Food and Drug Administration. Published online December 9, 2020. https://bit.ly/2KtYerG. Accessed February 13, 2021
Source link
