The Food and Drug Administration (FDA) has approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have received androgen receptor pathway inhibition and taxane-based chemotherapy. The FDA also approved a special radioactive diagnostic agent to assist in determining appropriate patients for the drug.

Pluvicto's efficacy was evaluated in a randomized (2:1), multicenter, open-label trial that compared Pluvicto plus best standard of care with best standard of care alone in men with progressive, PSMA-positive mCRPC. There was statistically significant improvement in overall survival and radiographic progression-free survival for those who received Pluvicto with best standard of care compared with those who received best standard of care alone. Median overall survival was 15.3 months in the intervention arm and 11.3 months in the control arm, although data interpretation may be limited owing to the number of dropouts from the control arm.

Pluvicto is a radioligand therapeutic agent. It binds with PSMA, a transmembrane protein expressed in prostate cancer, including mCRPC. The binding of Pluvicto allows delivery of radiation to PSMA-expressing cells as well as to surrounding cells, leading to DNA damage and cell death. The labeling warns that Pluvicto contributes to long-term cumulative radiation exposure in patients, which is associated with an increased risk of cancer.

Pluvicto's label also identifies these warnings and precautions: myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility. The most common adverse effects noted in the clinical trial were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities were hematologic changes, including decreased lymphocytes, hemoglobin, leukocytes, and platelets, and electrolyte changes, including decreased calcium and sodium.

Pluvicto's labeling recommends that nurses and other health care providers follow institutional radiation safety practices, patient treatment procedures, and Nuclear Regulatory Commission patient-release guidance, as well as provide instructions to the patient for follow-up radiation protection at home. Pluvicto can be administered as an injection with a syringe (with or without a syringe pump), as a gravity infusion (with or without an infusion pump), or directly from the vial with a peristaltic infusion pump.

Laboratory tests to assess for myelosuppression and kidney function should be performed before and during treatment. Men with partners of childbearing age should use effective contraception during treatment and for 14 weeks after the last dose. Nurses should also inform men that temporary or permanent infertility could result from treatment.

For complete prescribing information for Pluvicto, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf.