Vipivotide tetraxetan

Summary

Vipivotide tetraxetan (¹⁷⁷Lu-PSMA-617; Pluvicto) is an FDA- and EMA-approved radioligand therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). It combines a PSMA-targeting small molecule with DOTA chelator loaded with lutetium-177, delivering targeted radiotherapy to tumor sites. The VISION trial demonstrated significant improvements in radiographic progression-free survival and overall survival.

Mechanism of Action

Vipivotide tetraxetan is a PSMA (prostate-specific membrane antigen)-targeting ligand conjugated to the chelator DOTA, which binds lutetium-177 (¹⁷⁷Lu). Upon binding to PSMA-expressing prostate cancer cells, the complex is internalized, delivering targeted beta-particle radiation that induces DNA double-strand breaks and cell death in PSMA-positive tumor cells.

Routes of Administration

Goals & Uses

• Quality of life improvementOncology / Patient Reported OutcomesModerate
• Radiographic progression-free survival improvement in mCRPCOncology / Disease ControlHigh
• Overall survival improvement in mCRPCOncology / SurvivalHigh
• PSA response reductionOncology / Biomarker ResponseHigh
• Treatment of earlier-line PSMA-positive prostate cancerOncology / Expanding IndicationModerate

Contraindications

• PSMA-negative diseasePatient SelectionHigh
• Severely compromised bone marrow reserveHematologicHigh
• Severe renal impairmentOrganHighKidney function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data

Adverse Effects

• Dry mouth (xerostomia)Salivary Gland ToxicityCommon
• Myelosuppression (anemia, thrombocytopenia, leukopenia)HematologicCommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• NephrotoxicityRenalUncommon
• Radiation exposure to caregivers/publicRadiation SafetyCommon

Drug Interactions

• PSMA-targeting diagnostic agents (e.g., ¹⁸F-DCFPyL, ⁶⁸Ga-PSMA-11)Moderate
• Other myelosuppressive agents (e.g., chemotherapy)High
• Nephrotoxic agents (e.g., aminoglycosides, NSAIDs, contrast agents)Moderate

Population Constraints

• Patients with significant renal impairment (eGFR <30 mL/min)Renal FunctionRelative
• Women of childbearing potential / breastfeedingReproductiveAbsolute
• Pediatric patientsAgeAbsolute
• Patients with prior extensive pelvic radiationPrior TreatmentRelative

Regulatory Status

• European UnionApprovedApproved: PSMA-positive metastatic castration-resistant prostate cancer in adults who have received androgen receptor pathway inhibition and taxane-based chemotherapyEMA approved December 2022 under brand name Pluvicto. Centralized marketing authorization.
• United StatesApprovedApproved: PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in adults who have received androgen receptor pathway inhibition and taxane-based chemotherapyFDA approved March 23, 2022. REMS program required. Administered only in authorized nuclear medicine/oncology facilities.
• United KingdomApprovedApproved: PSMA-positive mCRPC in adults previously treated with ARPI and taxane-based chemotherapyMHRA approved; available through NHS England following NICE assessment; specialized radiopharmacy infrastructure required.

FDA approved March 2022 for PSMA-positive mCRPC in adults who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. EMA approved December 2022. Administered only in certified healthcare facilities due to radioactive nature. REMS program required in the US.

Evidence & Sources

No sources recorded yet.