Vipivotide tetraxetan
Also known as: ¹⁷⁷Lu-PSMA-617, 177Lu-vipivotide tetraxetan, AAA617, Lu-PSMA-617, Lu‑177 vipivotide tetraxetan, Pluvicto, PSMA-617, Vipivotide tetraxetan
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Summary
Vipivotide tetraxetan (Lu-177 PSMA-617, marketed as Pluvicto) is a radiolabelled small‑molecule that binds prostate‑specific membrane antigen (PSMA) and delivers beta‑particle radiation to PSMA‑expressing cancer cells. It is prescribed for patients with metastatic castration‑resistant prostate cancer (mCRPC) whose disease has progressed after prior systemic therapies.
Mechanism of Action
The molecule consists of a PSMA‑targeting ligand linked to the beta‑emitting radionuclide lutetium‑177. After intravenous infusion, the ligand binds with high affinity to PSMA on prostate cancer cells, is internalised, and the emitted beta particles cause DNA double‑strand breaks, leading to tumour cell death. The attached gamma emissions also permit imaging of distribution.
What the Research Shows
Randomised phase 3 trials have evaluated Lu‑177 PSMA-617 in mCRPC. In the VISION study, adding the radioligand to standard care improved radiographic progression‑free survival, overall survival, and delayed symptomatic skeletal events, while also preserving health‑related quality of life and reducing pain. Grade 3–4 haematologic toxicities (anemia, lymphopenia, thrombocytopenia) were more frequent, and treatment‑related deaths occurred in about 1% of patients. The PSMAfore trial, conducted in taxane‑naïve patients, showed similar delays in quality‑of‑life deterioration, pain worsening, and skeletal events, with anaemia the most common severe adverse event and no treatment‑related deaths reported. Both studies required PSMA‑positive disease confirmed by PET imaging.
Reported Benefits
Clinical data indicate that vipivotide tetraxetan can extend overall and progression‑free survival in heavily pre‑treated mCRPC, reduce the incidence of skeletal complications, and improve patient‑reported outcomes such as pain control and quality of life. The therapy offers a targeted approach that spares most normal tissues while delivering cytotoxic radiation to PSMA‑expressing tumours.
Limitations of the Evidence
Evidence is confined to phase 3 trials in PSMA‑positive metastatic prostate cancer, either after taxane exposure (VISION) or before taxane use (PSMAfore). Benefits have not been demonstrated in PSMA‑negative disease or earlier disease stages. Safety data reveal notable haematologic toxicity and rare fatal events. Long‑term outcomes and combination safety with other androgen‑targeted agents remain unevaluated.
Safety Considerations
The most common severe adverse events are anaemia, lymphopenia, and thrombocytopenia, occurring in up to half of treated patients. Treatment‑related deaths have been reported (approximately 1% in VISION) due to marrow failure or intracranial bleeding. Patients require regular blood‑count monitoring, and caution is advised in those with pre‑existing bone‑marrow compromise or extensive skeletal disease.
How It Is Administered
Vipivotide tetraxetan is given as an intravenous infusion of 7.4 GBq (200 mCi) every six weeks, typically for up to four cycles in the VISION protocol and up to six cycles in the PSMAfore protocol. Administration occurs in a nuclear‑medicine setting equipped for handling radiopharmaceuticals, with appropriate radiation safety measures.
Routes of Administration
Goals & Uses
- Quality of life improvementOncology / Patient Reported OutcomesModerate
- Metastatic castration‑resistant prostate cancer (mCRPC)OncologyHigh
- 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 impairment (eGFR <30 mL/min/1.73 m²)RenalModerate
- Known hypersensitivity to lutetium‑177 or DOTA‑based compoundsAllergicHigh
- Severe renal impairmentOrganHighKidney function concerns
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
Adverse Effects
- renal toxicityRenalUncommon
- Dry mouth (xerostomia)Salivary Gland ToxicityCommon
- Myelosuppression (anemia, thrombocytopenia, leukopenia)HematologicCommon
- Hematologic toxicity (anemia, thrombocytopenia, neutropenia)HematologicCommon
- NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
- FatigueGeneralCommonLow energy or tiredness
- Xerostomia (dry mouth)Salivary GlandCommon
- NephrotoxicityRenalUncommon
- Radiation exposure to caregivers/publicRadiation SafetyCommon
Drug Interactions
- Other myelosuppressive agentsModerate
- PSMA-targeting diagnostic agents (e.g., ¹⁸F-DCFPyL, ⁶⁸Ga-PSMA-11)Moderate
- Nephrotoxic drugs (e.g., cisplatin, NSAIDs)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
- Pregnant or lactating womenReproductiveAbsolute
- Patients with prior extensive pelvic radiationPrior TreatmentRelative
Regulatory Status
- European UnionApprovedApproved: PSMA‑positive metastatic castration‑resistant prostate cancerEMA approval (2023).
- United StatesApprovedApproved: PSMA‑positive metastatic castration‑resistant prostate cancerFDA approval (2022) under brand name Pluvicto.
- United KingdomApprovedApproved: PSMA‑positive metastatic castration‑resistant prostate cancerApproved by MHRA.
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
- Journal ArticleModerateSahu KK, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateFizazi K, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateFizazi K, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleModerateFallah J, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateKeam SJ2022-01-01T00:00:00.000000Z
- Journal ArticleModerateLiu X, et al.2023-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of cancer patients can receive vipivotide tetraxetan?
It is indicated for patients with metastatic castration‑resistant prostate cancer whose tumours express PSMA, as confirmed by PET imaging, and who have progressed after prior systemic therapies.
How does the treatment affect quality of life?
Phase 3 trials reported delayed worsening of health‑related quality‑of‑life scores, reduced pain intensity, and fewer symptomatic skeletal events compared with standard care alone.
What are the main side effects to watch for?
Significant haematologic toxicities—especially anemia, low lymphocyte and platelet counts—are common. Rarely, treatment‑related deaths have occurred due to marrow failure or bleeding, so blood monitoring is essential.
Can vipivotide tetraxetan be combined with other prostate‑cancer drugs?
Current data do not establish safety of concurrent use with many androgen‑receptor pathway inhibitors or other systemic agents; combination use should be approached cautiously and within clinical‑trial settings.
How is the drug administered?
It is delivered intravenously as a 7.4 GBq infusion every six weeks, typically for a series of four to six cycles, under the supervision of a nuclear‑medicine team.
What is Vipivotide tetraxetan?
Vipivotide tetraxetan (Lu-177 PSMA-617, marketed as Pluvicto) is a radiolabelled small‑molecule that binds prostate‑specific membrane antigen (PSMA) and delivers beta‑particle radiation to PSMA‑expressing cancer cells. It is prescribed for patients with metastatic castration‑resistant prostate cancer (mCRPC) whose disease has progressed after prior systemic therapies.
What is Vipivotide tetraxetan used for?
Vipivotide tetraxetan is educationally associated with: Quality of life improvement, Metastatic castration‑resistant prostate cancer (mCRPC), Radiographic progression-free survival improvement in mCRPC, Overall survival improvement in mCRPC, PSA response reduction, Treatment of earlier-line PSMA-positive prostate cancer. Educational only — not medical advice.
How is Vipivotide tetraxetan administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Vipivotide tetraxetan?
Reported adverse effects include: renal toxicity, Dry mouth (xerostomia), Myelosuppression (anemia, thrombocytopenia, leukopenia), Hematologic toxicity (anemia, thrombocytopenia, neutropenia), Nausea, Fatigue, Xerostomia (dry mouth), Nephrotoxicity, Radiation exposure to caregivers/public. This list is not exhaustive — consult a qualified clinician.
Who should avoid Vipivotide tetraxetan?
Recorded contraindications: PSMA-negative disease, Severely compromised bone marrow reserve, Severe renal impairment (eGFR <30 mL/min/1.73 m²), Known hypersensitivity to lutetium‑177 or DOTA‑based compounds, Severe renal impairment, Pregnancy. Consult a qualified clinician before use.