Lutetium Lu 177 Vipivotide Tetraxetan (Monograph)

Brand name: Pluvicto
Drug class: Antineoplastic Agents

Introduction

Lutetium lu 177 vipivotide tetraxetan is a radioligand therapeutic agent consisting of the radionuclide lutetium-177 linked to a moiety that binds to prostate-specific membrane antigen (PSMA), a transmembrane protein expressed in prostate cancer.

Uses for Lutetium Lu 177 Vipivotide Tetraxetan

Lutetium lu 177 vipivotide tetraxetan has the following uses:

Lutetium lu 177 vipivotide tetraxetan is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy, and are considered appropriate to delay taxane-based chemotherapy or have received prior taxane-based chemotherapy.

Lutetium Lu 177 Vipivotide Tetraxetan Dosage and Administration

General

Lutetium lu 177 vipivotide tetraxetan is available in the following dosage form(s) and strength(s):

Injection: 1,000 MBq/mL (27 mCi/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Select patients for treatment using LOCAMETZ or another approved PSMA positron emission tomography (PET) product based on PSMA expression in tumors.
Lutetium lu 177 vipivotide tetraxetan is a radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure. Use by or under the control of healthcare providers who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
Administer IV as an injection using the syringe method (as a slow IV push), as an infusion using the gravity method, or as an infusion using the peristaltic pump method. See Full Prescribing Information for specific instructions on these administration methods.
Recommended dosage is 7.4 GBq (equivalent to 200 mCi) IV every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity.
Dose interruption, reduction, or permanent discontinuation may be required due to adverse reactions.
Do not inject the lutetium lu 177 vipivotide tetraxetan solution directly into any other intravenous solution.
Management of adverse reactions may require temporary dose interruption, dose reduction, or permanent discontinuation of treatment.
See Full Prescribing Information for additional details on preparation and administration, and dosage modification recommendations for adverse reactions.

Cautions for Lutetium Lu 177 Vipivotide Tetraxetan

Contraindications

None.

Warnings/Precautions

Risk from Radiation Exposure

Lutetium lu 177 vipivotide tetraxetan contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer.

Minimize radiation exposure to patients, medical personnel, and others during and after treatment with lutetium lu 177 vipivotide tetraxetan consistent with institutional good radiation safety practices, patient treatment procedures, Nuclear Regulatory Commission patient-release guidance, and instructions to the patient for follow-up radiation protection at home.

Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation. Before the patient is released, inform patients about the necessary radioprotection precautions to follow to minimize radiation exposure to others.

After each administration of lutetium lu 177 vipivotide tetraxetan, advise patients to:

Limit close contact (less than 3 feet) with others for 2 days or with children and pregnant women for 7 days.
Refrain from sexual activity for 7 days.
Sleep in a separate room from others for 3 days, from children for 7 days, or from pregnant women for 15 days.

Myelosuppression

Lutetium lu 177 vipivotide tetraxetan can cause severe and life-threatening myelosuppression, including anemia, thrombocytopenia, leukopenia, and neutropenia.

In the PSMAfore study, Grade 3 or 4 decreased hemoglobin (7%), decreased leukocytes (4.4%), decreased neutrophils (3.5%), and decreased platelets (2.7%) occurred in patients treated with lutetium lu 177 vipivotide tetraxetan. One death occurred due to bone marrow failure during long-term follow-up in a patient who received lutetium lu 177 vipivotide tetraxetan.

In the VISION study, Grade 3 or 4 decreased hemoglobin (15%), decreased platelets (9%), decreased leukocytes (7%), and decreased neutrophils (4.5%) occurred in patients treated with lutetium lu 177 vipivotide tetraxetan. Grade ≥3 pancytopenia occurred in 1.1% (which includes two fatal events) of patients treated with lutetium lu 177 vipivotide tetraxetan. Two deaths (0.4%) occurred due to intracranial hemorrhage and subdural hematoma in association with thrombocytopenia, one death (0.2%) occurred due to sepsis and concurrent neutropenia, and one death (0.2%) occurred due to bone marrow failure.

Perform complete blood counts before and during treatment with lutetium lu 177 vipivotide tetraxetan. Withhold, reduce dose, or permanently discontinue lutetium lu 177 vipivotide tetraxetan based on the severity of myelosuppression.

Renal Toxicity

Lutetium lu 177 vipivotide tetraxetan can cause severe renal toxicity.

In the PSMAfore study, Grade 3 or 4 acute kidney injury (1.3%) occurred in patients treated with lutetium lu 177 vipivotide tetraxetan. In the VISION study, Grade 3 or 4 acute kidney injury (3.4%) occurred in patients treated with lutetium lu 177 vipivotide tetraxetan.

Advise patients to remain well hydrated and to urinate frequently before and after administration of lutetium lu 177 vipivotide tetraxetan. Perform kidney function laboratory tests, including serum creatinine and calculated creatinine clearance (CLcr), before and during treatment with lutetium lu 177 vipivotide tetraxetan. Withhold, reduce dose, or permanently discontinue lutetium lu 177 vipivotide tetraxetan based on the severity of renal toxicity.

Embryo-fetal Toxicity

The safety and efficacy of lutetium lu 177 vipivotide tetraxetan have not been established in females. Based on its mechanism of action, lutetium lu 177 vipivotide tetraxetan can cause fetal harm. No animal studies using lutetium Lu 177 vipivotide tetraxetan have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, radioactive emissions, including those from lutetium lu 177 vipivotide tetraxetan, can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception during treatment with lutetium lu 177 vipivotide tetraxetan and for 14 weeks after the last dose.

Infertility

Lutetium lu 177 vipivotide tetraxetan may cause infertility in males. The recommended cumulative dose of 44.4 GBq of lutetium lu 177 vipivotide tetraxetan results in a radiation absorbed dose to the testes within the range where lutetium lu 177 vipivotide tetraxetan may cause temporary or permanent infertility.

Specific Populations

Pregnancy

The safety and efficacy of lutetium lu 177 vipivotide tetraxetan have not been established in females. Based on its mechanism of action, lutetium lu 177 vipivotide tetraxetan can cause fetal harm. There are no available data on lutetium lu 177 vipivotide tetraxetan use in pregnant females. No animal studies using lutetium Lu 177 vipivotide tetraxetan have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radioactive emissions, including those from lutetium lu 177 vipivotide tetraxetan, can cause fetal harm.

Lactation

The safety and efficacy of lutetium lu 177 vipivotide tetraxetan have not been established in females. There are no data on the presence of lutetium Lu 177 vipivotide tetraxetan in human milk or its effects on the breastfed child or on milk production.

Females and Males Of Reproductive Potential

Advise males with female partners of reproductive potential to use effective contraception during treatment with lutetium lu 177 vipivotide tetraxetan and for 14 weeks after the last dose.

The recommended cumulative dose of 44.4 GBq of lutetium lu 177 vipivotide tetraxetan results in a radiation absorbed dose to the testes within the range where lutetium lu 177 vipivotide tetraxetan may cause temporary or permanent infertility.

Pediatric Use

The safety and effectiveness of lutetium lu 177 vipivotide tetraxetan in pediatric patients have not been established.

Geriatric Use

Of the 227 patients who received at least one dose of lutetium lu 177 vipivotide tetraxetan in the PSMAfore study, 177 patients (78%) were 65 years of age or older and 83 patients (37%) were 75 years of age or older. No overall differences in effectiveness were observed between patients ≥75 years of age and younger patients. Serious adverse reactions occurred in 20% of patients ≥75 years of age and in 20% of younger patients. Grade ≥3 adverse reactions occurred in 39% of patients ≥75 years of age and in 34% of younger patients.

Of the 529 patients who received at least one dose of lutetium lu 177 vipivotide tetraxetan plus best standard of care (BSoC) in the VISION study, 387 patients (73%) were 65 years of age or older and 143 patients (27%) were 75 years of age or older. No overall differences in effectiveness were observed between patients ≥75 years of age and younger patients. Serious adverse reactions occurred in 41% of patients ≥75 years of age and in 35% of younger patients. Grade ≥3 adverse reactions occurred in 56% of patients ≥75 years of age and in 53% of younger patients.

Renal Impairment

Exposure of lutetium Lu 177 vipivotide tetraxetan is expected to increase with the degree of renal impairment. No dose adjustment is recommended for patients with mild (baseline CLcr 60 to 89 mL/min by Cockcroft-Gault) to moderate (CLcr 30 to 59 mL/min) renal impairment; however, patients with mild to moderate renal impairment may be at greater risk of toxicity. Frequently monitor renal function and adverse reactions in patients with mild to moderate renal impairment. The pharmacokinetics and safety of lutetium lu 177 vipivotide tetraxetan have not been studied in patients with severe (CLcr 15 to 29 mL/min) renal impairment or end-stage renal disease.

Common Adverse Effects

Most common (≥ 20%) adverse reactions, including laboratory abnormalities, were decreased lymphocytes, decreased hemoglobin, fatigue, dry mouth, decreased platelets, decreased estimated glomerular filtration rate, nausea, decreased neutrophils, decreased calcium, decreased sodium, increased aspartate aminotransferase, increased alkaline phosphatase, arthralgia, decreased appetite, increased potassium, constipation, and back pain.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Lutetium Lu 177 vipivotide tetraxetan is a radioligand therapeutic agent. The active moiety of lutetium Lu 177 vipivotide tetraxetan is the radionuclide lutetium-177 which is linked to a moiety that binds to PSMA, a transmembrane protein that is expressed in prostate cancer, including mCRPC. Upon binding of lutetium Lu 177 vipivotide tetraxetan to PSMA-expressing cells, the beta-minus emission from lutetium-177 delivers radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage which can lead to cell death.

Advice to Patients

To minimize the risk from radiation exposure, ensure that patients increase their oral fluid intake and advise them to void as often as possible to reduce bladder radiation.
Before the patient is released, inform patients about the necessary radioprotection precautions to follow to minimize radiation exposure to others.
After each administration of lutetium lu 177 vipivotide tetraxetan, advise patients to limit close contact (less than 3 feet) with others for 2 days or with children and pregnant women for 7 days.
After each administration of lutetium lu 177 vipivotide tetraxetan, advise patients to refrain from sexual activity for 7 days.
After each administration of lutetium lu 177 vipivotide tetraxetan, advise patients to sleep in a separate room from others for 3 days, from children for 7 days, or from pregnant women for 15 days.
Advise patients to contact their healthcare provider for any signs or symptoms of myelosuppression, such as tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal or difficulty to stop bleeding, or frequent infections with signs, such as fever, chills, sore throat or mouth ulcers.
Because of the risk of renal toxicity, advise patients to remain well hydrated and to urinate frequently before and after administration of lutetium lu 177 vipivotide tetraxetan. Advise patients to contact their healthcare provider for any signs or symptoms of renal toxicity, such as passing urine less often than usual or passing much smaller amounts of urine than usual.
Advise males that lutetium lu 177 vipivotide tetraxetan can cause fetal harm.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with lutetium lu 177 vipivotide tetraxetan and for 14 weeks after the last dose.
Advise males of reproductive potential that lutetium lu 177 vipivotide tetraxetan may cause temporary or permanent infertility.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.