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.

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 3/4): 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 months 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 dose, reduce dose, or permanently discontinue LUTATHERA based on the 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 the reabsorption of lutetium Lu 177 dotatate through the proximal tubules and decrease the radiation dose to the kidneys. Advise patients to hydrate and to urinate frequently before, on the day of, and on the day after administration of LUTATHERA. Monitor serum creatinine and calculated creatinine clearance. Withhold dose, reduce dose, or permanently discontinue LUTATHERA based on the severity of renal toxicity. Patients with baseline renal impairment may be at increased risk of toxicity due to increased radiation exposure; perform more frequent assessments of renal function in patients with baseline mild or moderate impairment. LUTATHERA has not been studied in patients with baseline severe renal impairment (creatinine clearance <30 mL/min) or those with end-stage renal disease.
• 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, serum albumin, and the international normalized ratio during treatment. Withhold dose, reduce dose, or permanently discontinue LUTATHERA based on the severity of hepatotoxicity.
• 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 following LUTATHERA administration for a minimum of 2 hours in a setting in which cardiopulmonary resuscitation medication and equipment are available. Discontinue the infusion upon 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 1/2 hypersensitivity reactions to LUTATHERA before subsequent doses. Permanently discontinue LUTATHERA in patients who experience grade 3/4 hypersensitivity reactions.
• Neuroendocrine Hormonal Crisis: Neuroendocrine hormonal crises, 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 analogs, fluids, corticosteroids, and electrolytes as indicated.
• Embryo-Fetal Toxicity: LUTATHERA can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating LUTATHERA. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LUTATHERA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LUTATHERA and for 4 months after the last dose.
• 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 3/4 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%), increased 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 analogs competitively bind to somatostatin receptors and may interfere with the efficacy of LUTATHERA. Discontinue long-acting somatostatin analogs 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.

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

SPECIFIC POPULATIONS

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

Please see full Prescribing Information.