Posluma

POSLUMA is 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.

• Recommended amount of radioactivity of POSLUMA is 296 MBq (8 mCi) administered as an intravenous bolus injection. (
  
  
  
  2.2 Recommended Dose and Administration Instructions

  Recommended Dose

  The recommended amount of radioactivity to be administered in adults is 296 MBq (8 mCi) as an intravenous bolus injection.

  Preparation and Administration Instructions

  • Inspect POSLUMA visually for particulate matter and discoloration before administration. Do not use the drug if the solution contains particulate matter or is discolored.
  • Use aseptic technique and radiation shielding when withdrawing and administering POSLUMA.
  • Calculate the necessary volume to administer based on calibration time and required dose.
  • The recommended maximum volume of undiluted POSLUMA is 5 mL.
  • POSLUMA may be diluted with 0.9% Sodium Chloride Injection, USP.
  • Assay the dose in a dose calibrator before administration.

  Post Administration Instructions

  • After the POSLUMA injection, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection, USP to ensure full delivery of the dose.
  • Dispose of any unused drug in a safe manner in compliance with applicable regulations.
  )
  
  
• Initiate imaging approximately 60 minutes after administration. Scanning should start from mid-thigh and proceed to base of skull. (
  
  
  
  2.4 Image Acquisition

  • Patients should void immediately prior to imaging.
  • Position the patient supine with arms above the head.
  • Begin image acquisition approximately 60 minutes after POSLUMA injection.
  • Image acquisition should start from mid-thigh and proceed to the base of the skull.
  • Scan duration is approximately 20 minutes depending on the number of bed positions and acquisition time per bed position (typically 3 minutes). Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible.
  )
  
  
• See full prescribing information for additional preparation, handling, administration, imaging, and radiation dosimetry information. (
  
  
  
  2.3 Patient Preparation

  Instruct patients to drink water prior to administration of POSLUMA to ensure adequate hydration and to continue drinking and voiding frequently for the first few hours following administration to reduce radiation exposure.
  ,
  
  
  
  2.4 Image Acquisition

  • Patients should void immediately prior to imaging.
  • Position the patient supine with arms above the head.
  • Begin image acquisition approximately 60 minutes after POSLUMA injection.
  • Image acquisition should start from mid-thigh and proceed to the base of the skull.
  • Scan duration is approximately 20 minutes depending on the number of bed positions and acquisition time per bed position (typically 3 minutes). Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible.
  )
  
  

Injection: 296 MBq/mL to 5,846 MBq/mL (8 mCi/mL to 158 mCi/mL) as flotufolastat F 18 gallium in approximately 25 mL at end of synthesis supplied as a clear, colorless solution in a multiple-dose vial.

POSLUMA is not indicated for use in females. There are no available data on the use of POSLUMA in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with flotufolastat F 18. Radioactive drugs, including POSLUMA, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose.

• Risk of Image Misinterpretation: Image interpretation errors can occur with POSLUMA imaging. Interpretation of POSLUMA PET may differ depending on imaging readers in patients with suspected recurrence of prostate cancer. Consider multidisciplinary consultation and histopathological confirmation. (
  
  
  
  5.1 Risk of Image Misinterpretation

  Image interpretation errors can occur with POSLUMA PET. 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 POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping

  [See Clinical Studies ]

  . The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels

  [See Clinical Studies ]

  . Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended.

  Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence

  The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region

  [see Clinical Studies ].

  Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline.
  ,
  
  
  
  14.2 Imaging for Suspected Recurrence of Prostate Cancer

  The safety and efficacy of POSLUMA were evaluated in SPOTLIGHT (NCT04186845), a prospective, multicenter, open-label, single-arm study in patients with biochemical evidence of recurrent prostate cancer.

  The study enrolled 391 patients with suspected recurrence defined by either serum PSA of at least 0.2 ng/mL after radical prostatectomy (with confirmatory PSA level also at least 0.2 ng/mL) or by an increase in serum PSA of at least 2 ng/mL above the nadir after other therapies.

  All patients received a single dose of POSLUMA with an administered radioactivity (mean ± SD) of 306 ± 22 MBq (8.27 ±0.61 mCi), followed by PET/CT scan from mid-thigh to base of the skull. Three central readers blinded to clinical information independently interpreted each scan by region for the presence and location of lesions considered positive for prostate cancer

  [see Dosage and Administration ]

  . The regions interpreted were grouped into three for primary analysis: prostate/prostate bed; pelvic lymph nodes; and other (including extra-pelvic lymph nodes, bone, and soft tissue/parenchyma).

  A total of 389 patients had an evaluable POSLUMA PET scan. The mean age was 68 years (range: 43 to 86 years); distribution by race was 75% White, 16% Black or African American, 4% other, and 5% unreported; and distribution by ethnicity 5% was Hispanic/Latino, 87% non-Hispanic/Latino, and 8% unreported. The median baseline serum PSA level was 1.1 ng/mL with 60% of patients having a baseline PSA <2.0 ng/mL. Prior treatment included radical prostatectomy in 79% of the patients.

  POSLUMA-positive interpretations were compared to a reference standard of either histopathology or other imaging (CT, MRI, Technetium 99m bone scan, or fluciclovine F 18 PET) obtained within 90 days of the POSLUMA scan using a lesion-to-lesion co-localization method and separate consensus panel. Reference standard information for negative interpretations was not collected.

  At least one POSLUMA-positive lesion was detected by at least one reader in 366 patients (94%). Reference standard information consisted of imaging only (n=297) or histopathology (n=69). As a percentage of patients with an evaluable scan, 51% (95% CI: 46% to 56%) for reader 1, 48% (95% CI: 43% to 53%) for reader 2, and 49% (95% CI: 44% to 54%) for reader 3 had at least one matching positive region between the POSLUMA scan and the reference standard. Of all POSLUMA-positive regions, 46% (95% CI: 42% to 50%) for reader 1, 60% (95% CI: 55% to 66%) for reader 2, and 53% (95% CI: 48% to 58%) for reader 3 were categorized as positive by the reference standard.

  Table 7shows patient-level results from the majority read stratified by serum PSA level. Percent PET positivity was calculated as the percentage of patients with POSLUMA-positive lesions out of all patients with an evaluable PET scan. Percent PET positivity includes true and false positives and is not a measure of diagnostic performance.

  Table 7: Patient-Level POSLUMA PET Results and Percent PET Positivity Stratified by Serum PSA Level in SPOTLIGHT by Majority Read (N=389)

  PSA = prostate-specific antigen, PA = positive agreement, NPA = no positive agreement, CI = confidence interval
  aImaging comprised of one or more of the following: CT, MRI,99mTc Bone Scan, fluciclovine F 18 PET
  PSA (ng/mL)	N	PET Positive Patients					PET Negative Patients	Percent PET Positivity [95% CI]
  		Total	Histopathology		Imaging only a
  			PA	NPA	PA	NPA
  < 0.5	121	77	6	4	27	40	44	64% [54,72]
  ≥ 0.5 and < 1	67	51	7	3	24	17	16	76% [64,86]
  ≥ 1 and < 2	45	42	10	2	18	12	3	93% [82, 99]
  ≥ 2	156	152	33	3	84	32	4	97% [94, 99]
  Total	389	322	56	12	153	101	67	83% [79, 86]

  Variable Interpretation in Patients with Suspected Prostate Cancer Recurrence

  POSLUMA reader agreement was evaluated for the three central readers and 389 patients. Inter-reader Fleiss ϰ was 0.41 (95% CI: 0.39-0.43). The three readers agreed on the presence or absence of positive lesions across all five evaluated regions in 118 patients (30% unanimity)

  [see Warning and Precautions ].

  Given the level of inter-reader agreement observed overall, POSLUMA reader agreement was further evaluated by regional subgroup. The Fleiss ϰ for was 0.40 (95% CI: 0.33-0.46) in the prostate/prostate bed, 0.73 (95% CI: 0.67-0.78) in the pelvic lymph nodes, and 0.62 (95% CI: 0.58-0.65) across the other regions.
  )
  
  
• Radiation risk: POSLUMA contributes to a patient's long-term cumulative radiation exposure. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure. (
  
  
  
  2.1 Radiation Safety - Drug Handling

  Handle POSLUMA with safety measures to minimize radiation exposure

  [

  see

  Warnings and Precautions ]

  . Use waterproof gloves, effective radiation shielding, including syringe shields, and other appropriate safety measures when handling and administering POSLUMA.

  Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides.
  ,
  
  
  
  5.2 Radiation Risks

  POSLUMA use contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers

  [see Dosage and Administration ]

  .
  )