Current guidelines recognize that estrogen receptor heterogeneity contributes to endocrine therapy resistance. In metastatic disease, estrogen receptor discordance between primary and metastatic lesions may be present in up to 60% of patients (NCCN Guidelines Breast Cancer).
Hoefnagel et al. suggest that changes in biomarker status between primary and secondary lesions could impact treatment and patient survival rates. Discordance in estrogen receptor status between lesions was shown in 15.1% of patients (Hoefnagel et al., 2010). Furthering this observation, Amir et al. evaluate the impact of receptor status change on patient management in two prospective studies comprising biopsies of recurrent lesions. Tissue was analyzed for estrogen receptors and progesterone receptors by immunohistochemical staining, as well as HER2 by fluorescence in situ hybridization. A total of 289 patients underwent biopsy. Discordance in ER primary and recurrent lesions was 12.6% (p < 0.001). Biopsy results influenced the management of 14.2% of patients (p ≤ 0.0001) who had undergone biopsy (Amir et al., 2011).
Based on guideline recognition and the aforementioned papers, capturing changes in biomarker status between primary and secondary lesions can impact patient survival rate. Therefore, a medical need exists to evaluate estrogen receptor expression across metastatic tumor burden. Given the ability to visualize ER expression and assess the entire body, Cerianna™ (fluoroestradiol F 18)* may very well be poised to fulfil this unmet need. With a Cerianna scan, patients may be stratified into three groups: purely estrogen receptor-positive disease, purely estrogen receptor-negative disease, and heterogeneic disease. This information may provide actionable information to health care providers to improve the quality of care of their patients.
Cerianna's capability to assign patients to after mentioned categories is highlighted in a retrospective study involving 91 patients with metastatic breast cancer using 18F-FES (Nienhuis et al., 2018). 18F-FES PET/CT scans were performed over five years, with each patient having biopsy-proven estrogen receptor-positive primary or metastatic breast cancer. An SUV of greater than 1.5 was used to define estrogen receptor positivity. 49% of patients had purely estrogen receptor-positive disease; 12% of patients had purely estrogen receptor-negative disease; 36% of patients had heterogenic disease. Illustrating the broad and comprehensive characterization provided by 18F-FES PET, these classifications were based on a median of 9 lesions per patient.
The potential for Cerianna to aid clinicians’ therapy selection does exist for patients with estrogen receptor-positive metastatic breast cancer. Linden et al. studied the impact of 18F-FES imaging on management with endocrine therapy. 47 patients with estrogen receptor-positive recurrent or metastatic breast cancer lesions were evaluated (Linden et al., 2006). Both 18F-FES and Fludeoxyglucose F 18 Injection (18F-FDG)** PET scans were performed prior to treatment initiation and followed by an 18F-FDG PET scan post-treatment. Again, an SUV of 1.5 was used to qualify tumors as estrogen receptor-positive versus estrogen receptor-negative. Zero out of fifteen patients with initial SUV less than 1.5 responded to hormonal therapy, compared to eleven out of 32 patients with SUV higher than 1.5 that did respond to hormonal therapy (p < 0.01).
Advancing the claim that Cerianna impacts therapy selection, Boers et al. identified 30 patients with metastatic breast cancer that could benefit from endocrine treatment (Boers et al., 2020). 18F-FES positive lesions responded to therapy and resulted in a near-complete metabolic response. In comparison, 18F-FES negative lesions resulted in little to no metabolic response with pathologic uptake in new lesions. In addition, although limited by sample size, a trend for improved progression free survival was observed in patients with 100% estrogen receptor-positive disease versus patients with estrogen receptor-negative or heterogeneic disease, further highlighting the potential of assessing whole-body disease burden.
Additionally, an interesting study by Sun et al. identified 33 patients who underwent 18F-FES PET to resolve the evaluation of equivocal lesions on conventional imaging (Sun et al. 2015). An example case presented in the paper, a CT scan detected a new lung lesion in a known breast cancer patient. Health care providers were unable to determine whether this lesion was primary lung cancer or breast cancer metastasis, which was 18F-FDG avid. An 18F-FES scan resolved the ambiguity by showing unequivocal uptake of 18F-FES in the lesion, thereby suggested metastatic breast cancer tissue, which was confirmed following a surgical procedure. Cerianna, by virtue of visualization of estrogen receptors, may address clinical dilemmas in estrogen receptor-positive breast cancer pertaining to equivocal and/or ambiguous findings on conventional imaging.
Cerianna can discriminate between estrogen receptor-positive and estrogen receptor-negative tumors, and can provide the equivalent of a whole-body biopsy for estrogen receptors in patients with recurrent or metastatic breast cancer. Compared to tissue assays with limited sampling, Cerianna can better demonstrate the estrogen receptor status of the burden of disease. Imaging estrogen receptors with Cerianna may provide supplementary data that can assist with therapy selection.
CERIANNA™ is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) imaging for the detection of ER (ER)-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer.
Limitations of Use
Tissue biopsy should be used to confirm recurrence of breast cancer and to verify ER status by pathology. CERIANNA™ is not useful for imaging other receptors, such as human epidermal growth factor receptor 2 (HER2) and the progesterone receptor (PR).
IMPORTANT SAFETY INFORMATION
- Adverse Reactions – Reported adverse reactions include: injection site pain and dysgeusia
- Radiation Risks – Ensure safe drug handling and patient preparation procedures to protect patients and health care providers from unintentional radiation exposure.
- Risk of Misdiagnosis – Do not use CERIANNA™ in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer.
- Contraindications – None.
- Use in Specific Populations – Lactation: Interrupt breastfeeding. Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA™ administration
To report SUSPECTED ADVERSE REACTIONS, contact Zionexa US Corp at +1.844.946.6392 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DOSAGE AND ADMINISTRATION
- Recommended dose is 222 MBq (6 mCi), with a range of 111 MBq to 222 MBq (3 mCi to 6 mCi), administered as an intravenous injection over 1 to 2 minutes.
- Recommended imaging start time is 80 minutes (range 20 minutes to 80 minutes) after drug administration.
- See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information.
DOSAGE FORMS AND STRENGTHS
Injection: 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL) of fluoroestradiol F 18 in a multiple-dose vial.
You can find the full prescribing information here: https://www.cerianna.com/wp-content/uploads/2020/05/cerianna-prescribing-information.pdf
**INDICATIONS AND USAGE
Fludeoxyglucose F 18 Injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings:
- Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
- Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.
- Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.
IMPORTANT SAFETY INFORMATION
Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.
Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to ensure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.
Adverse Reactions: Hypersensitivity reactions with pruritus, edema, and rash have been reported. Have emergency resuscitation equipment and personnel immediately available.
DOSAGE FORMS AND STRENGTHS:
Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) Fludeoxyglucose F 18 Injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration.
Fludeoxyglucose F 18 Injection is manufactured and distributed by PETNET Solutions, Inc., 810 Innovation Drive, Knoxville, TN39732
You can find the full prescribing information here: