IMPORTANT SAFETY INFORMATION AND INDICATION

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IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Radiation Exposure: Treatment with LUTATHERA contributes to a patient’s overall long-term cumulative radiation exposure and is associated with an increased risk for cancer. Radiation can be detected in the urine for up to 30 days following LUTATHERA administration. Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with LUTATHERA consistent with institutional good radiation safety practices, patient management procedures, Nuclear Regulatory Commission patient release guidance, and instructions to the patient for follow-up radiation protection at home.

INDICATION

LUTATHERA^® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Mechanism of Action

Overview

LUTATHERA Is the First FDA-Approved RLT for the Treatment of Adult Patients With SSTR-Positive GEP-NETs¹

LUTATHERA

Somatostatin Receptor Expression

GEP-NETs Overexpress SSTR Subtype 2²

of GEP-NETs have been demonstrated to express SSTRs, with 86% expressing SSTR subtype 2^2,a,b

^aBased on a study of 100 cases with clinical and pathological data selected from a prospectively built database of patients with gastroenteropancreatic endocrine tumors referred from 3 institutions.²

^bThis work was supported by grants from Novartis.

Patients with GEP-NETs with a high density of SSTR expression may be considered for targeted treatment with LUTATHERA.^3,4

With a high affinity for SSTR subtype 2, LUTATHERA is designed to deliver beta radiation to SSTR-expressing cells, including SSTR-positive tumor cells.³

Mechanism of Action for LUTATHERA

LUTATHERA is a targeted treatment that uses radiation to damage SSTR-positive cells and neighboring cells.³

PRECISION TARGETING FOR
SSTR-POSITIVE CELLS³

Illustration of LUTHERA targeting components finding cells with SSTRs.

LUTATHERA contains a targeting component that helps find cells with SSTRs, including GEP-NET cancer cells.

Illustration of LUTHERA binding to SSTRs located outside of the cells.

Once it finds these target cells, LUTATHERA binds to the SSTRs located on the outside of the cells.

ENTERS THE CELLS³

Illustration of LUTHERA entering the cell.

After LUTATHERA binds to the SSTRs, it enters into the cell.

Illustration of LUTHERA delivering radiation.

LUTATHERA delivers radiation that causes damage to the SSTR-positive cells and nearby cells.

LUTATHERA is a peptide receptor radionuclide that binds to SSTRs on the surface of cells that express this receptor.³

FDA, US Food and Drug Administration; GEP-NETs, gastroenteropancreatic neuroendocrine tumors; RLT, radioligand therapy; SSA, somatostatin analogue; SSTR, somatostatin receptor.

Next: Access

References: 1. Advanced Accelerator Applications receives FDA approval for Lutathera^® for treatment of gastroenteropancreatic neuroendocrine tumors [news release]. East Hanover, NJ: Novartis Pharmaceuticals Corp; January 26, 2018. https://www.novartis.com/news/media-releases/advanced-accelerator-applications-receives-fda-approval-lutathera-treatment-gastroenteropancreatic-neuroendocrine-tumors. Accessed April 15, 2022. 2. Zamora V, Cabanne A, Salanova R, et al. Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours. Dig Liver Dis. 2010;42(3):220-225. 3. Lutathera [prescribing information]. Millburn, NJ: Advanced Accelerator Applications. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Neuroendocrine and Adrenal tumors V.3.2021. © National Comprehensive Cancer Network, Inc. 2021 All rights reserved. Accessed September 29, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

INDICATION

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Radiation Exposure: Treatment with LUTATHERA contributes to a patient’s overall long-term cumulative radiation exposure and is associated with an increased risk for cancer. Radiation can be detected in the urine for up to 30 days following LUTATHERA administration. Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with LUTATHERA consistent with institutional good radiation safety practices, patient management procedures, Nuclear Regulatory Commission patient release guidance, and instructions to the patient for follow-up radiation protection at home.
Myelosuppression: In the NETTER-1 clinical trial, myelosuppression occurred more frequently in patients receiving LUTATHERA with long-acting octreotide compared with patients receiving high-dose long-acting octreotide (all grades/grade 3 or 4): anemia (81%/0 vs 54%/1%), thrombocytopenia (53%/1% vs 17%/0), and neutropenia (26%/3% vs 11%/0). In NETTER-1, platelet nadir occurred at a median of 5.1 weeks following the first dose. Of the 59 patients who developed thrombocytopenia, 68% had platelet recovery to baseline or normal levels. The median time to platelet recovery was 2 months. Fifteen of the 19 patients in whom platelet recovery was not documented had post-nadir platelet counts. Among these 15 patients, 5 improved to grade 1, 9 to grade 2, and 1 to grade 3. Monitor blood cell counts. Withhold, reduce dose, or permanently discontinue based on severity of myelosuppression.
Secondary Myelodysplastic Syndrome and Leukemia: In NETTER-1, with a median follow-up time of 76 months in the main study, myelodysplastic syndrome (MDS) was reported in 2.3% of patients receiving LUTATHERA with long-acting octreotide compared with no patients receiving high-dose long-acting octreotide. In ERASMUS, a phase 2 clinical study, 16 patients (2.0%) developed MDS and 4 (0.5%) developed acute leukemia. The median time to onset was 29 months (range, 9-45 months) for MDS and 55 months (range, 32-125 months) for acute leukemia.
Renal Toxicity: In ERASMUS, 8 patients (<1%) developed renal failure 3 to 36 months following LUTATHERA. Two of these patients had underlying renal impairment or risk factors for renal failure (eg, diabetes or hypertension) and required dialysis. Administer the recommended amino acid solution before, during, and after LUTATHERA to decrease reabsorption of lutetium Lu 177 dotatate through the proximal tubules and decrease the radiation dose to the kidneys. Do not decrease the dose of the amino acid solution if the dose of LUTATHERA is reduced. Advise patients to urinate frequently during and after administration of LUTATHERA. Monitor serum creatinine and calculated creatinine clearance. Withhold, reduce dose, or permanently discontinue LUTATHERA based on severity of renal toxicity. Patients with baseline renal impairment may be at greater risk of toxicity; perform more frequent assessments of renal function in patients with mild or moderate impairment. LUTATHERA has not been studied in patients with severe renal impairment (creatinine clearance <30 mL/min).
Hepatotoxicity: In ERASMUS, 2 patients (<1%) were reported to have hepatic tumor hemorrhage, edema, or necrosis, with 1 patient experiencing intrahepatic congestion and cholestasis. Patients with hepatic metastasis may be at increased risk of hepatotoxicity due to radiation exposure. Monitor transaminases, bilirubin, and serum albumin during treatment. Withhold, reduce dose, or permanently discontinue LUTATHERA based on severity of hepatic impairment.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, occurred in patients treated with LUTATHERA. Monitor patients closely for signs and symptoms of hypersensitivity reactions, including anaphylaxis, during and after LUTATHERA administration for a minimum of 2 hours in a setting in which cardiopulmonary resuscitation medication and equipment are available. Discontinue the infusion at the first observation of any signs or symptoms consistent with a severe hypersensitivity reaction and initiate appropriate therapy. Premedicate patients with a history of grade 1 or 2 hypersensitivity reactions to LUTATHERA before subsequent doses. Permanently discontinue LUTATHERA in patients who experience grade 3 or 4 hypersensitivity reactions.
Neuroendocrine Hormonal Crisis: Neuroendocrine hormonal crisis, manifesting with flushing, diarrhea, bronchospasm, and hypotension, occurred in <1% of patients in ERASMUS and typically occurred during or within 24 hours following the initial LUTATHERA dose. Two (<1%) patients were reported to have hypercalcemia. Monitor patients for flushing, diarrhea, hypotension, bronchoconstriction, or other signs and symptoms of tumor-related hormonal release. Administer intravenous somatostatin analogues, fluids, corticosteroids, and electrolytes as indicated.
Embryo-Fetal Toxicity: LUTATHERA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the final dose. Verify pregnancy status of females of reproductive potential prior to initiating LUTATHERA.
Risk of Infertility: LUTATHERA may cause infertility in males and females. Radiation absorbed by testes and ovaries from the recommended cumulative LUTATHERA dose falls within the range in which temporary or permanent infertility can be expected following external beam radiotherapy.

ADVERSE REACTIONS

The most common grade 3 to 4 adverse reactions (≥4% with a higher incidence in the LUTATHERA arm) observed in NETTER-1 were lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea (5%), elevated aspartate aminotransferase (5%), increased alanine aminotransferase (4%), hyperglycemia (4%), and hypokalemia (4%).

In ERASMUS, the following serious adverse reactions have been observed with a median follow-up time of >4 years after treatment with LUTATHERA: myelodysplastic syndrome (2%), acute leukemia (1%), renal failure (2%), hypotension (1%), cardiac failure (2%), myocardial infarction (1%), and neuroendocrine hormonal crisis (1%). Patients should be counseled and monitored in accordance with the LUTATHERA Prescribing Information.

DRUG INTERACTIONS

Somatostatin and its analogues competitively bind to somatostatin receptors and may interfere with the efficacy of LUTATHERA. Discontinue long-acting somatostatin analogues at least 4 weeks and short-acting octreotide at least 24 hours prior to each LUTATHERA dose. Administer short- and long-acting octreotide during LUTATHERA treatment as recommended.

Corticosteroids can induce downregulation of subtype 2 somatostatin receptors. Avoid repeated administration of high doses of glucocorticosteroids during treatment with LUTATHERA.

SPECIFIC POPULATIONS

Lactation: Because of the potential risk for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with LUTATHERA and for 2.5 months after the final dose.

Please see full Prescribing Information.