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Lutetium Lu-177 dotatate

Lu-177 DOTATATE · 177Lu-DOTATATE · Lutathera · Bexlutry

Lutetium Lu-177 dotatate is a radioactive prescription treatment for gastroenteropancreatic neuroendocrine tumors that express somatostatin receptors. LUTATHERA is the US product described here.

FDA

In NETTER-1, Lu-177 dotatate plus long-acting octreotide improved progression-free survival versus high-dose octreotide in selected adults with progressive midgut tumors. The final overall survival comparison was not statistically significant.

PMID 28076709PMID 34793718

By the Peptides Media Editorial TeamEditorial policy4 min read

PurposeTargeted radiation treatment
FDA
TargetSomatostatin receptors
FDA
Labeled scheduleFour doses, about eight weeks apart
FDA
Key safetyBone marrow and kidneys
FDA

Overview

Quick answer

Lu-177 dotatate is a treatment, while gallium-68 dotatate is a PET imaging agent. Lu-177 vipivotide tetraxetan is another treatment with a different target, PSMA, and a different labeled use.

FDA: LUTATHERA prescribing informationFDA: NETSPOT prescribing informationFDA: PLUVICTO prescribing information

Who is included in the LUTATHERA US indication?

Adults and pediatric patients aged 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut and hindgut tumors.

FDA

What did NETTER-1 show?

The estimated percentage without progression or death at 20 months was 65.2% with Lu-177 dotatate plus octreotide versus 10.8% with high-dose octreotide. The trial enrolled patients with progressive midgut tumors.

PMID 28076709

Did NETTER-1 establish longer overall survival?

Its final overall survival analysis did not show a statistically significant difference. Progression-free survival and overall survival measure different outcomes.

PMID 34793718

How is LUTATHERA given?

The label specifies 7.4 GBq (200 mCi) intravenously every 8 weeks, plus or minus 1 week, for four doses, with amino acid infusion, antiemetics, octreotide timing and monitoring as described in the label.

FDA

Evidence

Evidence snapshot

US indicationLUTATHERA for receptor-positive GEP tumors

The LUTATHERA label applies to adults and children aged 12 years and older.

FDA
NETTER-1Progression-free survival

In 229 patients in the primary analysis, the estimated 20-month progression-free survival rates were 65.2% versus 10.8%.

PMID 28076709
NETTER-1 follow-upOverall survival not significant

The final analysis reported median overall survival of 48.0 versus 36.3 months; the difference was not statistically significant.

PMID 34793718
SafetyMonitoring required

Marrow suppression, kidney and liver toxicity, hormonal crisis and secondary blood cancers are among the label warnings.

FDA

Claims

Common claims vs evidence

ClaimHuman evidenceVerdict
Lu-177 dotatate slows progression in certain neuroendocrine tumors.NETTER-1 compared the drug plus octreotide with higher-dose octreotide in patients whose receptor-positive midgut tumors had progressed on prior octreotide. Supported for the trial population; the study did not test every GEP tumor setting.
PMID 28076709
A progression-free survival benefit proves longer overall survival.The final NETTER-1 overall survival analysis did not reach statistical significance, even though the earlier progression endpoint favored treatment. Not established by the final overall survival comparison.
PMID 28076709PMID 34793718
The two Lu-177 cancer treatments work on the same target.Lu-177 dotatate binds somatostatin receptors. Lu-177 vipivotide tetraxetan binds PSMA and is labeled for different prostate cancer settings. No. The shared isotope does not make the targeting molecules or indications interchangeable.
FDA: LUTATHERA prescribing informationFDA: PLUVICTO prescribing information

Bottom line

Main takeaway

Treatment, not a scan

LUTATHERA delivers radiation to receptor-bearing tissue and is given by a specialized clinical team.

FDA
Treatment tradeoffs

The treatment can delay progression in selected tumors but also has important marrow, kidney and other risks.

PMID 28076709FDA
Trial population

NETTER-1 studied progressive receptor-positive midgut tumors after octreotide, not all labeled GEP tumors.

PMID 28076709FDA

Identity

What it is

LUTATHERA is a lutetium-177-labeled somatostatin analog used in peptide receptor radionuclide therapy. Receptor binding targets radiation to tissue, but normal tissues can also be exposed.

FDA

The LUTATHERA label covers receptor-positive gastroenteropancreatic neuroendocrine tumors in adults and children aged 12 years and older. BEXLUTRY is another Lu-177 dotatate product with an adult label.

FDA: LUTATHERA prescribing informationFDA: BEXLUTRY prescribing information

Use context

Routes, doses, and cycle patterns

LUTATHERA dosing is measured as radioactive activity rather than peptide mass. The treating team may interrupt, reduce or stop treatment for adverse reactions.

FDA

Human studies and product labels

LUTATHERA labeled schedule

Purpose
Treatment of eligible receptor-positive GEP neuroendocrine tumors
Context
US prescribing information
Route
Intravenous infusion by qualified personnel
Amount
7.4 GBq (200 mCi) per dose
Frequency
Every 8 weeks, plus or minus 1 week
Duration
Four doses

The label specifies antiemetics and an intravenous lysine and arginine infusion for kidney protection, with monitoring and dose modifications for adverse reactions. The amounts are radioactivity, not milligrams.

FDA

NETTER-1 study regimen

Purpose
Compare progression-free survival in progressive midgut tumors
Context
Randomized controlled trial
Route
Intravenous infusion
Amount
7.4 GBq (200 mCi) per dose
Frequency
Every 8 weeks, plus long-acting octreotide
Duration
Four infusions

The comparison group received long-acting octreotide 60 mg every 4 weeks.

PMID 28076709

What varies

  • The label starts the amino acid infusion 30 minutes before LUTATHERA and continues it during and for at least 3 hours after the infusion. An antiemetic is given before the amino acid solution.
    FDA
  • Long-acting somatostatin analogs and short-acting octreotide have specified intervals before each treatment. Long-acting octreotide is administered 4 to 24 hours after each LUTATHERA dose under the label. The clinical team coordinates this timing.
    FDA
  • Blood counts, kidney function and liver tests are monitored, and pregnancy status is checked when applicable.
    FDA
  • The LUTATHERA label advises hydration and frequent urination before, on the day of, and the day after each administration.
    FDA

Research

Research evidence

NETTER-1 found an advantage in progression-free survival for Lu-177 dotatate plus octreotide over high-dose octreotide in progressive midgut disease. The final overall survival comparison was not statistically significant.

PMID 28076709PMID 34793718
Study / evidence areaPopulationDesignProduct contextMain outcomeLimitationsWeight
NETTER-1 primary analysis
PMID 28076709
229 patients with well-differentiated progressive metastatic midgut tumorsOpen-label randomized phase 3 trial with blinded progression assessmentLu-177 dotatate plus octreotide versus high-dose long-acting octreotideEstimated progression-free survival at 20 months was 65.2% versus 10.8%; objective response rates were 18% versus 3%. Patients had receptor-positive midgut tumors progressing on octreotide; the result should not be treated as a cure or generalized to every tumor site. Randomized, population-specific
NETTER-1 final overall survival analysis
PMID 34793718
Randomized patients with advanced receptor-positive midgut tumorsPrespecified final overall survival and long-term safety analysisLu-177 dotatate plus octreotide versus high-dose octreotideMedian overall survival was 48.0 versus 36.3 months; hazard ratio 0.84.The comparison did not reach statistical significance. Progression-free survival and overall survival cannot be treated as interchangeable. Randomized follow-up, overall survival not significant

Use context

Reported use context

NETTER-1 compared Lu-177 dotatate plus octreotide with higher-dose octreotide in progressive midgut tumors.

PMID 28076709

Study and label context

01
NETTER-1 randomized trialIntravenous infusion

7.4 GBq (200 mCi) every 8 weeks for four infusions, with long-acting octreotide.

Adults with progressive receptor-positive midgut neuroendocrine tumors.
PMID 28076709

Cautions

Safety and unknowns

  • Myelosuppression can reduce blood counts. Myelodysplastic syndrome and leukemia have also occurred after treatment; monitoring continues under the treating team's plan.
    FDA
  • Kidney and liver toxicity can occur despite supportive care. The label calls for kidney and liver monitoring and dose changes when needed. It specifies more frequent kidney assessments in patients with mild or moderate baseline kidney impairment because toxicity risk may be higher.
    FDA
  • The label states that LUTATHERA's safety and how the body processes it have not been studied in patients with severe baseline kidney impairment or end-stage kidney disease, or in pediatric patients aged 12 and older with baseline kidney impairment.
    FDA
  • Hypersensitivity, including anaphylaxis, and neuroendocrine hormonal crisis are serious risks. The label calls for monitoring after administration.
    FDA
  • Treatment contributes to radiation exposure and can cause fetal harm or infertility. The label includes pregnancy, contraception and breastfeeding precautions.
    FDA

Product quality

Product identity and quality

LUTATHERA is a radioactive prescription injection handled by clinicians trained in radiopharmaceutical safety. The prescribed activity is verified for administration and is not a conventional peptide mass dose.

FDA

The BEXLUTRY label specifies adults and omits the pediatric use included in the LUTATHERA label. Confirm the exact product and its labeling.

FDA: LUTATHERA prescribing informationFDA: BEXLUTRY prescribing information

Supportive medications

Amino acid infusion, antiemetics and octreotide scheduling are specific parts of the labeled treatment.

FDA

Mechanism

How it is proposed to work

The dotatate component binds somatostatin receptors, carrying radioactive lutetium-177 to receptor-bearing tissue. Its radiation can damage cells.

FDA
01

The drug binds with highest affinity to somatostatin receptor subtype 2. Lutetium-177 emits beta radiation; exposure is not confined to tumor cells.

FDA

Details

Technical details

Lutetium Lu-177 dotatate technical details
Radiopharmaceutical
Lutetium Lu-177 dotatate
FDA
US product
LUTATHERA
FDA
Target
Somatostatin receptors
FDA
Label activity
7.4 GBq (200 mCi) per dose
FDA

Sources

References

  1. 1.

    FDA. LUTATHERA prescribing information

    US prescribing information for receptor-positive gastroenteropancreatic neuroendocrine tumors, administration and safety.

  2. 2.

    PubMed. Phase 3 trial of Lu-177 dotatate for midgut neuroendocrine tumors

    doi:10.1056/NEJMoa1607427 PMID:28076709 NCT01578239

    Primary analysis of NETTER-1, comparing Lu-177 dotatate plus octreotide with high-dose octreotide.

  3. 3.

    PubMed. NETTER-1 final overall survival and long-term safety analysis

    doi:10.1016/S1470-2045(21)00572-6 PMID:34793718 NCT01578239

    Prespecified final overall survival analysis and long-term safety follow-up.

  4. 4.

    FDA. NETSPOT prescribing information

    US label for the distinct gallium-68 dotatate imaging agent.

  5. 5.

    FDA. PLUVICTO prescribing information

    US label for the distinct PSMA-targeted Lu-177 treatment.

  6. 6.

    FDA. BEXLUTRY prescribing information

    US label for a second Lu-177 dotatate product, with an adult indication.