Lantheus Announces Presentation at the 2021 American Urological Association (AUA) Annual Meeting
Highlights Piflufolastat F 18’s Potential to Change Initial Risk Assessment and Intended Patient Management in High-Risk Prostate Cancer
Identified Regional Lymph Node and/or Distant Metastases in 26.9% of Patients Prior to Definitive Therapy
The OSPREY study evaluated the diagnostic performance of piflufolastat F 18 PET/CT using a histopathology truth standard in men with newly diagnosed prostate cancer. A single dose of 9 mCi (333 MBq) of piflufolastat F 18 was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. 268 men with a median PSA 9.7 (range 1.2-125.3, n=267) underwent a piflufolastat F 18 PET/CT scan. After a piflufolastat F 18 PET/CT scan, 72 (26.9%) patients had regional lymph node and/or distant metastases identified and were radiographically staged with 39 (14.6%) as N1/M0 and 33 (12.3%) as N0/M1 or N1/M1 disease.
In addition, the Company also presented at the meeting the results of an independent, retrospective review to assess the impact of piflufolastat F 18 imaging on the planned management of the patients in the trial. A multidisciplinary panel, consisting of an independent urologist, medical oncologist and radiation oncologist, assessed the patients’ clinical profiles and conventional imaging data before reviewing the patients’ piflufolastat F 18 imaging data. Incorporation of the piflufolastat F 18 results led to a potential change in planned management for 43.6% (115/264) of patients. In 39.0% (103/264), a change in surgery or type of surgery was recommended and in 25.8% (68/264), a change in planned radiation therapy was recommended.1
“In the OSPREY trial, in patients selected for radical prostatectomy, piflufolastat F 18 was able to detect disease outside of the prostate in nearly one-third of the cases,” said
“Proper patient selection for any therapy is critical,” said
OSPREY Phase 2/3 Trial
The OSPREY trial was designed to assess the diagnostic performance of piflufolastat F 18 to detect prostate cancer in pelvic lymph nodes in subjects with high-risk, locally advanced prostate cancer (Cohort A). The primary endpoints for the trial were sensitivity and specificity of piflufolastat F 18 PET/CT imaging to detect metastatic prostate cancer within the pelvic lymph nodes relative to histopathology in Cohort A.
OSPREY enrolled a cohort of 268 men with biopsy-proven prostate cancer who were considered candidates for radical prostatectomy and pelvic lymph node dissection. These patients were all considered to have high risk disease based on criteria such as Gleason score, PSA level, and tumor stage. Each patient received a single piflufolastat F 18 PET/CT scan from mid-thigh to skull vertex.
Three central readers independently interpreted each PET scan for the presence of abnormal piflufolastat F 18 uptake in pelvic lymph nodes in multiple sub-regions, including the common iliac lymph nodes. The readers were blinded to all clinical information. While readers also recorded the presence of piflufolastat F 18 PET-positive lesions in the prostate gland and outside the pelvis, those results were not included in the primary efficacy analysis.
A total of 252 patients (94%) underwent standard-of-care prostatectomy and template pelvic lymph node dissection and had sufficient histopathology data for evaluation of the pelvic lymph nodes. Surgical specimens were separated into three regions: left hemipelvis, right hemipelvis, and other. For each patient, piflufolastat F 18 PET results and histopathology results obtained from dissected pelvic lymph nodes were compared by surgical region. PET results in locations that were not dissected were excluded from analysis.
For the 252 evaluable patients, the mean age was 64 years (range 46 to 84 years), and 87% were white. The median serum PSA was 9.3 ng/mL. The total Gleason score was 7 for 19%, 8 for 46%, and 9 for 34% of the patients, with the remainder of the patients having Gleason scores of 6 or 10.
In the trial, the diagnostic performance of piflufolastat F 18 in detecting disease in pelvic lymph nodes (Cohort A) was compared with histopathology. When matched by lymph node location, piflufolastat F 18 showed specificity of 95-98%, sensitivity of 28-39%, and positive predictive value (PPV) of 72-81% meeting the specificity but not the pre-established sensitivity co-primary endpoint.
Safety results showed piflufolastat F 18 was well tolerated. The most frequent adverse events reported were dysgeusia (2.6%), headache (1.8%) and fatigue (1.3%).2
About Prostate Cancer
Prostate cancer is the second most common form of cancer affecting men in
About PYLARIFY® (piflufolastat F 18) Injection
PYLARIFY (piflufolastat F 18) injection (also known as 18F-DCFPyL or PyL) is a fluorinated small molecule PSMA-targeted PET imaging agent that enables visualization of lymph nodes, bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer. For men with prostate cancer, PYLARIFY PET combines the accuracy of PET imaging, the precision of PSMA targeting and the clarity of an F 18 radioisotope for superior diagnostic performance. The recommended PYLARIFY dose is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi), administered as a bolus intravenous injection.4-9
PYLARIFY® (piflufolastat F 18) Injection
PYLARIFY® (piflufolastat F 18) Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.
Important Safety Information
Warnings and Precautions
Risk of Image Misinterpretation
Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. The performance of PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage. PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.
Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may be delayed. Always have trained staff and resuscitation equipment available.
Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.
The most frequently reported adverse reactions were headaches, dysgeusia and fatigue, occurring at rate of ≤2% during clinical studies with PYLARIFY. In addition, a delayed hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reactions.
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.
To report suspected adverse reactions for PYLARIFY, call 1-800-362-2668 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For important risk and use information about PYLARIFY Injection, please see Full Prescribing information.
Safe Harbor for Forward-Looking and Cautionary Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, that are subject to risks and uncertainties and are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements may be identified by their use of terms such as “anticipate,” “believe,” “confident,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “will” and other similar terms. Such forward-looking statements are based upon current plans, estimates and expectations that are subject to risks and uncertainties that could cause actual results to materially differ from those described in the forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Readers are cautioned not to place undue reliance on the forward-looking statements contained herein, which speak only as of the date hereof. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law. Risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements include (i) the Company’s ability to successfully launch PYLARIFY as a commercial product, including (A) Lantheus’ ability to obtain FDA approval for additional PET manufacturing facilities (PMFs) that could manufacture PYLARIFY, (B) the ability of those PMFs to supply PYLARIFY to customers, and (C) Lantheus’ ability to sell PYLARIFY to customers; and (ii) the risks and uncertainties discussed in our filings with the
1Changes in treatment plan do not necessarily lead to improved patient outcomes.
2Pienta KJ 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). J Urol. 2021;206(1):52-61.
4Mena et al. 18 F-DCFPyL PET/CT Imaging in Patients with Biochemically Recurrent Prostate Cancer After Primary Local Therapy J Nucl Med 2020 Jun;61(6):881-889. doi: 10.2967/jnumed.119.234799. Epub 2019
5Alipour et al. Guiding management of therapy in prostate cancer: time to switch from conventional imaging to PSMA PET? Ther Adv Med Oncol. 2019; 11: 1758835919876828.
6Werner et al 18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging Theranostics 2020; 10(1):1-16. doi:10.7150/thno.37894.
7Petersen LJ, Zacho HD. PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review. Cancer Imaging. 2020;20(1):1-8. doi:10.1186/s40644-020-0290-
8Tan N, Oyoyo U, Bavadian N, et al. PSMA-targeted radiotracers versus 18F fluciclovine for the detection of prostate cancer biochemical recurrence after definitive therapy: a systematic review and meta-analysis. Radiology. 2020;296:44-55. doi:10.1148/radiol.2020191689
9PYLARIFY® [package insert].
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Director, Corporate Communications
Source: Lantheus Medical Imaging