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Lutetium Lu-177 vipivotide tetraxetan

Lu-177 PSMA-617 · 177Lu-PSMA-617 · Pluvicto

Lutetium Lu-177 vipivotide tetraxetan is a radioactive medicine that targets prostate-specific membrane antigen, or PSMA. The US product PLUVICTO treats certain adults with PSMA-positive metastatic prostate cancer.

FDA

In VISION, previously treated patients with PSMA-positive metastatic castration-resistant prostate cancer had longer median overall survival when Lu-177 PSMA-617 was added to protocol-permitted standard care. Other disease stages and treatment histories have separate evidence and label criteria.

PMID 34161051FDA

By the Peptides Media Editorial TeamEditorial policy4 min read

PurposeTargeted radiation treatment
FDA
TargetPSMA
FDA
Labeled scheduleUp to six doses, six weeks apart
FDA
Key safetyBone marrow, kidneys and dry mouth
FDA

Overview

Quick answer

PLUVICTO is a treatment, not the PSMA PET imaging drug used to help select patients. It is also different from Lu-177 dotatate, which targets somatostatin receptors in certain neuroendocrine tumors.

FDA: PLUVICTO prescribing informationFDA: LUTATHERA prescribing information

Which prostate cancer settings are in the US label?

For PSMA-positive metastatic androgen pathway modulation-naive or modulation-sensitive disease, the label specifies use with an androgen receptor pathway inhibitor, or ARPI. For modulation-resistant disease, patients must have received an ARPI and be considered appropriate to delay taxane chemotherapy or have received a prior taxane.

FDA

How are patients selected?

The label specifies an approved PSMA PET product to assess PSMA expression. The imaging product and PLUVICTO are different medicines.

FDA

How is it given?

The label describes 7.4 GBq (200 mCi) intravenously every 6 weeks for six doses, or until progression or unacceptable toxicity. Adverse reactions may require a delay, reduction or discontinuation. The label also calls for a concurrent gonadotropin-releasing hormone (GnRH) analog or prior surgical removal of both testicles.

FDA

What did VISION measure?

In patients previously treated with an ARPI and taxane chemotherapy, median overall survival was 15.3 months with the added radioligand and 11.3 months with standard care alone.

PMID 34161051

Evidence

Evidence snapshot

VISIONOverall survival, 15.3 vs 11.3 months

The comparison was in previously treated PSMA-positive metastatic castration-resistant disease.

PMID 34161051
PSMAforeRadiographic progression-free survival

In selected patients without prior taxane treatment for metastatic castration-resistant disease, the primary analysis reported a median of 9.3 versus 5.55 months against a change in ARPI.

PMID 39293462
PSMAdditionEarlier metastatic disease

Adding Lu-177 PSMA-617 to androgen deprivation and an ARPI improved radiographic progression-free survival in an interim analysis; median progression-free survival had not been reached in either group.

PMID 42561994
SafetyRadiation and organ monitoring

The label warns about marrow suppression, kidney toxicity, fetal harm and infertility.

FDA

Claims

Common claims vs evidence

ClaimHuman evidenceVerdict
PLUVICTO is appropriate for every person with prostate cancer.The label requires PSMA-positive metastatic disease and specifies separate conditions for androgen pathway modulation-naive or modulation-sensitive and modulation-resistant settings. No. PSMA imaging, disease state and treatment history matter.
FDA
VISION established longer survival in previously treated metastatic disease.VISION compared Lu-177 PSMA-617 plus protocol-permitted standard care against standard care alone after an ARPI and taxane treatment. Supported in the studied population, not proof of cure or an individual prediction.
PMID 34161051
A progression benefit in hormone-sensitive disease proves longer overall survival.The PSMAddition interim analysis reported radiographic progression-free survival. That endpoint is different from overall survival. The reported interim progression result does not establish an overall survival benefit.
PMID 42561994
All treatments labeled with Lu-177 are interchangeable.PLUVICTO targets PSMA; Lu-177 dotatate targets somatostatin receptors. Their indications and supportive care differ. No. Isotope, targeting molecule, indication and product must all be identified.
FDA: PLUVICTO prescribing informationFDA: LUTATHERA prescribing information

Bottom line

Main takeaway

What it does

PLUVICTO is a radiation treatment for selected PSMA-positive metastatic prostate cancers, not a scan.

FDA
Selection and monitoring

PSMA PET, disease history, blood counts and kidney function are relevant to treatment decisions and monitoring.

FDA

Identity

What it is

Lu-177 vipivotide tetraxetan, also called Lu-177 PSMA-617, is a PSMA-binding small-molecule radioligand attached to radioactive lutetium-177. It is not the somatostatin analog dotatate.

FDA: PLUVICTO prescribing informationFDA: LUTATHERA prescribing information

The label identifies separate indications for metastatic androgen pathway modulation-naive or modulation-sensitive prostate cancer and metastatic androgen pathway modulation-resistant prostate cancer. In the first setting, use is combined with an ARPI; in the second, prior treatment requirements apply.

FDA

Use context

Routes, doses, and cycle patterns

PLUVICTO activity is measured in GBq or mCi. The label specifies patient selection, accompanying medicines and treatment changes for adverse reactions.

FDA

Human studies and product labels

PLUVICTO labeled schedule

Purpose
Treatment of eligible PSMA-positive metastatic prostate cancer
Context
US prescribing information
Route
Intravenous injection or infusion by qualified personnel
Amount
7.4 GBq (200 mCi) per dose
Frequency
Every 6 weeks
Duration
Six doses, or until progression or unacceptable toxicity

The modulation-naive or modulation-sensitive indication requires an ARPI. The modulation-resistant indication has prior ARPI and taxane-related eligibility criteria. The label provides dose modifications for adverse reactions.

FDA

VISION trial regimen

Purpose
Overall survival and imaging-based progression-free survival
Context
Randomized trial after ARPI and taxane treatment
Route
Intravenous infusion
Amount
7.4 GBq (200 mCi) per dose
Frequency
Every 6 weeks, with protocol-permitted standard care
Duration
Four to six doses, subject to trial criteria

The comparison group received protocol-permitted standard care alone.

PMID 34161051FDA

PSMAddition trial regimen

Purpose
Radiographic progression-free survival in earlier metastatic disease
Context
Randomized trial of androgen pathway modulation-naive or modulation-sensitive disease
Route
Intravenous administration
Amount
7.4 GBq (200 mCi) per dose
Frequency
Every 6 weeks, with androgen deprivation and an ARPI
Duration
Up to six cycles

The control group received androgen deprivation and an ARPI without the radioligand.

PMID 42561994

What varies

  • The label calls for patient selection using an approved PSMA PET product and assessment of blood counts and kidney function before and during treatment.
    FDA
  • Radiation safety precautions, hydration and frequent urination are part of the label. After each dose, it advises limiting close contact within 3 feet of other people for 2 days, and of children and pregnant people for 7 days.
    FDA
  • After each dose, the label also advises avoiding sexual activity for 7 days and sleeping in a separate room from others for 3 days, children for 7 days, and pregnant people for 15 days.
    FDA
  • The label says patients receiving PLUVICTO for metastatic prostate cancer should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or have had bilateral orchiectomy. An ARPI is also part of the modulation-naive or modulation-sensitive indication.
    FDA

Research

Research evidence

VISION reported longer overall survival after prior ARPI and taxane treatment. PSMAfore studied patients selected to delay taxane chemotherapy after an ARPI, while PSMAddition studied an earlier metastatic setting with androgen deprivation and an ARPI. Progression and survival outcomes are distinct.

PMID 34161051PMID 39293462PMID 42561994
Study / evidence areaPopulationDesignProduct contextMain outcomeLimitationsWeight
VISION
PMID 34161051FDA
831 patients with PSMA-positive metastatic castration-resistant prostate cancer after an ARPI and taxane treatmentOpen-label randomized phase 3 trialLu-177 PSMA-617 plus protocol-permitted standard care versus standard care aloneAmong all 831 randomized patients, median overall survival was 15.3 versus 11.3 months. In the 581-patient imaging analysis, median progression-free survival was 8.7 versus 3.4 months. The trial was open-label. Early dropout in the control arm limits interpretation of the size of the imaging-based progression benefit. Randomized, previously treated population
PSMAfore
PMID 39293462FDA
468 selected patients with metastatic castration-resistant prostate cancer after an ARPI and without prior taxane treatment for metastatic resistant diseaseOpen-label randomized phase 3 trial, with crossover after progressionLu-177 PSMA-617 versus a change in ARPIAt the primary analysis, median radiographic progression-free survival was 9.30 versus 5.55 months, with a hazard ratio of 0.41. Crossover was permitted. The final overall survival comparison described in the label was not statistically significant. Randomized, progression endpoint
PSMAddition
PMID 42561994
1,144 patients with PSMA-positive metastatic androgen pathway modulation-naive or modulation-sensitive prostate cancerOpen-label randomized phase 3 trial, second interim progression analysisLu-177 PSMA-617 plus androgen deprivation and an ARPI versus androgen deprivation and an ARPIThe hazard ratio for radiographic progression or death was 0.72; the median was not reached in either group. Grade 3 or worse adverse events occurred in 51% versus 43% of treated patients. The reported interim progression result does not establish a longer overall survival. Results do not predict an individual patient's response. Randomized, interim progression endpoint

Use context

Reported use context

VISION and PSMAddition studied different patient groups and accompanying treatments.

PMID 34161051PMID 42561994

Study and label context

01
VISIONIntravenous infusion

7.4 GBq (200 mCi) every 6 weeks for four to six cycles, plus protocol-permitted standard care.

Metastatic castration-resistant prostate cancer after an ARPI and taxane treatment.
PMID 34161051
02
PSMAdditionIntravenous administration

7.4 GBq (200 mCi) every 6 weeks for up to six cycles, with androgen deprivation and an ARPI.

PSMA-positive metastatic androgen pathway modulation-naive or modulation-sensitive prostate cancer.
PMID 42561994

Cautions

Safety and unknowns

  • Myelosuppression can cause low blood counts and serious complications. Complete blood counts are checked before and during treatment.
    FDA
  • Kidney toxicity can be severe. The label calls for hydration, frequent urination and kidney function testing, with treatment changes when needed.
    FDA
  • Patients with mild or moderate baseline kidney impairment may have a higher risk of toxicity. The label calls for frequent checks of kidney function and adverse reactions in this group. Safety and drug exposure have not been studied in patients with severe kidney impairment (creatinine clearance 15 to 29 mL/min) or end-stage kidney disease.
    FDA
  • Fatigue, dry mouth and nausea are among reported adverse reactions. Low blood counts can also appear as laboratory abnormalities.
    FDA
  • Radiation exposure requires precautions to protect the patient and others. The drug may cause fetal harm and temporary or permanent infertility; the label includes contraception guidance.
    FDA

Product quality

Product identity and quality

PLUVICTO is a prescription radioactive injection. Qualified providers measure its activity and use radiation shielding and handling precautions.

FDA

Imaging selection

A PSMA PET product is used to select patients; it is not the treatment injection.

FDA

Mechanism

How it is proposed to work

The targeting part binds PSMA, which can be present on prostate cancer cells. Lutetium-177 emits radiation that can damage nearby cells.

FDA
01

The molecule consists of a PSMA-binding ligand, a chelator and lutetium-177. Uptake in normal tissues means treatment is not free of radiation-related toxicity.

FDA

Details

Technical details

Lutetium Lu-177 vipivotide tetraxetan technical details
Radiopharmaceutical
Lutetium Lu-177 vipivotide tetraxetan
FDA
Other name
Lu-177 PSMA-617
PMID 34161051
Target
Prostate-specific membrane antigen
FDA
Label activity
7.4 GBq (200 mCi) per dose
FDA

Sources

References

  1. 1.

    FDA. PLUVICTO prescribing information

    US prescribing information including PSMA-positive metastatic androgen pathway modulation-naive or modulation-sensitive and modulation-resistant indications.

  2. 2.

    PubMed. Lu-177 PSMA-617 for metastatic castration-resistant prostate cancer: VISION

    doi:10.1056/NEJMoa2107322 PMID:34161051 NCT03511664

    Randomized VISION trial after androgen receptor pathway inhibitor and taxane treatment.

  3. 3.

    PubMed. PSMAfore randomized trial in taxane-naive metastatic castration-resistant prostate cancer

    doi:10.1016/S0140-6736(24)01653-2 PMID:39293462 NCT04689828

    Randomized trial of Lu-177 PSMA-617 versus a change in androgen receptor pathway inhibitor.

  4. 4.

    PubMed. PSMAddition randomized trial in metastatic androgen pathway modulation-naive or modulation-sensitive prostate cancer

    doi:10.1016/S0140-6736(26)01092-5 PMID:42561994 NCT04720157

    Randomized trial adding Lu-177 PSMA-617 to androgen deprivation and an androgen receptor pathway inhibitor.

  5. 5.

    FDA. LUTATHERA prescribing information

    US label for the distinct somatostatin receptor-targeted Lu-177 treatment.