Lutetium Lu 177 vipivotide tetraxetan (also known as Lu-177–PSMA-617 or by the brand name Pluvicto) is a novel radiopharmaceutical used in the treatment of advanced prostate cancer. It was FDA-approved in 2022.
Mechanism of Action
This therapy consists of a radioactive isotope, Lutetium-177, bound to a targeting ligand, PSMA-617. Its function includes:
- Targeting PSMA: It binds to Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is over-expressed on the cell surface of over 90% of prostate cancers.
- Selective Radiation: Once bound, it selectively delivers beta-particle radiation directly to PSMA-positive cells and their immediate microenvironment, causing cellular damage.
Clinical Indications and Usage
Lutetium-177 PSMA is specifically indicated for patients with PSMA-positive metastatic castration-resistant prostate cancer (m1CRPC) who meet the following criteria:
- Prior Treatment: They must have been previously treated with at least one novel hormonal therapy (androgen-receptor pathway inhibitor) and one taxane-based chemotherapy.
- PSMA Positivity: Patients must have at least one PSMA-positive lesion or metastatic disease that is primarily PSMA-positive as identified by PSMA-targeted PET imaging.
Administration and Dosing
- Dosage: The standard dose is 7.4 GBq (200 mCi) administered intravenously.
- Schedule: It is given every 6 weeks for up to a maximum of 6 doses.
Clinical Trial Evidence
- VISION Trial (Phase III): This study found that adding Lu-PSMA-617 to standard care significantly improved overall survival (15.3 vs. 11.3 months) and progression-free survival (8.7 vs. 3.4 months) compared to standard care alone.
- TheraP Trial (Phase II): In a comparison with cabazitaxel, Lu-PSMA-617 demonstrated a higher PSA response rate (66% vs. 37%) and a more favorable safety profile regarding certain side effects like diarrhea.
Side Effects and Safety
Common toxicities associated with the treatment include fatigue, dry mouth (xerostomia), nausea, anemia, decreased appetite, and constipation or diarrhea. More serious risks include renal toxicity and myelosuppression (bone marrow suppression).
Patient Precautions: Due to the radioactivity, patients are advised to limit close contact with others (especially children and pregnant women) for up to 7 days following a dose.