A GUIDE TONURSING CARE

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 INFORMATION1 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. Please see additional Important Safety Information throughout and accompanying full Prescribing Information.

LUTATHERA treatment requires collaboration of a multidisciplinary team2

Procedures at specific institutions may vary.

Medical oncology practice Nuclear medicine or

radiation oncology practice

• Disease progression identified in a patientwith GEP-NETs on first-line somatostatinanalog (SSA)

• Patient evaluated for treatment withLUTATHERA

• Decision made to treat with LUTATHERA

• Long-acting SSA discontinued ≥4 weeksprior to LUTATHERA administration

• Short-acting SSA, if needed for symptommanagement, discontinued ≥24 hoursprior to LUTATHERA administration

• Pretreatment screening laboratory testsordered and determined to be withinacceptable limits

• Long-acting octreotide administered 4 to24 hours after each LUTATHERA dose

• Patient is followed for adverse reactions,laboratory abnormalities, and tumorchanges

• Long-acting octreotide 30 mg monthlycontinued until disease progression orfor up to 18 months after LUTATHERAtreatment initiation

• Continuing monitoring for response,progression, and adverse reactions

• Nuclear imaging test isperformed to determine whetherthe GEP-NETs are somatostatinreceptor positive

• Patient treated with LUTATHERA,given discharge instructions, andreleased

Treatment cycle repeats 4 times at 8-week intervals

What is LUTATHERA?

• LUTATHERA is a targeted radioligand therapy (RLT)

• LUTATHERA targets somatostatinreceptor-positive GEP-NETs usingradiation to induce damage tocancer cells that are positive forthe somatostatin hormone receptor.Some neighboring cells may beaffected as well1

• It is administered throughintravenous (IV) infusion1

The role of LUTATHERA in your patient’s treatment journey

IMPORTANT SAFETY INFORMATION1WARNINGS AND PRECAUTIONS (continued) Myelosuppression: In NETTER-1 clinical trial, myelosuppression occurred more frequently in patients receiving LUTATHERA with long acting octreotide at the following rates (all grades/grade 3 or 4): anemia (81%/0), thrombocytopenia (53%/1%), and neutropenia (26%/3%). Blood cell counts must be monitored prior to, during, and after treatment. Withhold, reduce dose, or permanently discontinue based on severity of myelosuppression.Please see additional Important Safety Information throughout and accompanying full Prescribing Information.

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LUTATHERA is a targeted RLT1,3

• LUTATHERA is a radionuclide (177Lu) linked to a somatostatin analog, which bindssomatostatin receptors that are expressed on the surface of GEP-NET cells1

• Because LUTATHERA works by binding somatostatin receptors, an imaging testis performed to determine whether somatostatin receptors (SSTRs) are present onthe patient’s tumor cells

Percentage of GEP-NETs Expressing Somatostatin Receptors (N=100)4

% o

f P

atie

nts

Po

siti

ve

86%

46%

26% 24%

62%

100

80

60

40

20

0SSTR1 SSTR2 SSTR3 SSTR4 SSTR5

Study included 67 gastrointestinal NETs, 25 pancreatic NETs, and 8 liver metastases of unknown origin. Receptor expression was determined by immunohistochemistry.4

Reprinted from Dig Liver Dis. 42(3):220-225. Zamora V, et al. © 2010, with permission from Elsevier.

• The density of SSTR expression is higher on GEP-NETs than on nontumor tissues5

• LUTATHERA binds with the highest affinity to SSTR21

How LUTATHERA works1

dotatate(somatostatin

analog)

LUTATHERA

LUTATHERA is infusedintravenously

Once in the body, LUTATHERAbinds somatostatin receptorson GEP-NET cells

LUTATHERA is internalizedand emits beta radiation,causing damage to the celland neighboring cells

1

2

3

4

Lu 177(radionuclide)

LUTATHERA delivers targeted radiation to GEP-NET cells

Please see additional Important Safety Information throughout and accompanying full Prescribing Information.

NET, neuroendocrine tumor.

IMPORTANT SAFETY INFORMATION1WARNINGS AND PRECAUTIONS (continued) Secondary Myelodysplastic Syndrome and Leukemia: In NETTER-1, with a median follow-up time of 24 months, myelodysplastic syndrome (MDS) was reported in 2.7% of patients receiving LUTATHERA with long-acting octreotide. In ERASMUS, a Phase II clinical study, 16 patients (2.0%) developed MDS and 4 (0.5%) developed acute leukemia. The median time to the development of MDS was 28 months (9 to 41 months) and 55 months (32 to 155 months) for acute leukemia.

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Radiation exposure is common from other sources, for example:

Approximately 3,000 μSv annually from natural background radiation8

14.5 μSv on a 5.2-hour flight from Los Angeles to Honolulu9

Radiation associated with LUTATHERA treatment is within recommended limits• LUTATHERA is a beta emitter that decays with a half-life of 6.647 days1 and emits

2 types of radiation6:

− A low-to-medium-energy β particle, which is predominantly absorbed withinthe patient’s body

− γ radiation at a low quantity and low-to-medium energy

• The maximum radiation penetration in tissue is 2.2 mm, and the mean penetrationis 0.67 mm1

• Patients are discharged from the treatment center only when radiation exposureto third parties does not exceed regulatory thresholds2

• For HCPs and caregivers, exposure to LUTATHERA is less than the naturalbackground radiation acquired during 1 year7,8

Results of a Study Performed to Evaluate the Safety of Outpatient Treatment With Lutetium Lu 177 Dotatate by Measurement of

Radiation Exposures of HCPs and Caregivers7

Methods Results

• 76 patients with progressive,metastatic NETs received 4 cyclesof 7.8 GBq lutetium Lu 177 dotatateat 8-week intervals in an outpatientsetting

• 4 patients were treated in 1 room, witheach patient remaining until radiationexposure was below the release limit

• Radiation exposures to HCPs andcaregivers were monitored bypersonal dosimeter

• Mean whole-body exposures pertherapy day for HCPs administeringLUTATHERA ranged from 6.8 μSv(nuclear medicine technologist) to33.2 μSv (nurse)

• Mean total exposure to 25 caregiversduring the day of therapy and at homefor a period of up to 5 days was90 μSv, with a median exposure of40 μSv and range of 10 μSv to470 μSv

• Exposures to HCPs, caregivers,and family members were withinthe limits recommended by theInternational Commission onRadiological Protection

Radiation exposure

Important safety instructions1

• Radiopharmaceuticals, including LUTATHERA, should be used by or under thecontrol of HCPs who are qualified by specific training and experience in the safeuse and handling of radiopharmaceuticals, and whose experience and training havebeen approved by the appropriate governmental agency authorized to license theuse of radiopharmaceuticals

• Use waterproof gloves and effective radiation shielding when handling LUTATHERA

• Verify pregnancy status of females of reproductive potential prior to initiatingLUTATHERA

HCP, healthcare professional.

IMPORTANT SAFETY INFORMATION1

WARNINGS AND PRECAUTIONS (continued) Renal Toxicity: Treatment with LUTATHERA will expose kidneys to radiation, which may impair renal function. In ERASMUS <1% of patients developed renal failure 3 to 36 months following LUTATHERA. Monitor serum creatinine and creatinine clearance to assess changes in renal function. Advise patients to urinate frequently during and after administration of LUTATHERA. A concomitant intravenous infusion of amino acids before, during and after LUTATHERA administration is mandatory for renal protection. 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. Withhold, reduce dose, or permanently discontinue based on severity of renal toxicity. Do not decrease the dose of amino acid solution if the dose of LUTATHERA is reduced. LUTATHERA has not been studied in patients with severe renal impairment (CrCL < 30 mL/min).

Please see additional Important Safety Information throughout and accompanyingfull Prescribing Information.

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What patients can expect during LUTATHERA treatment

LUTATHERA is given as a defined, 4-dose treatment regimen1

8 16 24

TOTAL LUTATHERA

ADMINISTERED(29.6 GBq/800 mCi)

weeks

weeks

weeks

weeks

18months*

LUTATHERA200 mCi

Long-actingoctreotide 30 mg

Long-actingoctreotide 30 mg

LUTATHERA200 mCi

Long-actingoctreotide 30 mg

LUTATHERA200 mCi

Long-actingoctreotide 30 mg

LUTATHERA200 mCi

Long-actingoctreotide 30 mg

0

LUTATHERA Treatment Regimen

*Continue long-acting octreotide 30 mg every 4 weeks after completing LUTATHERA until disease progression or for up to18 months following treatment initiation.1

• The recommended LUTATHERA dosage is 7.4 GBq (200 mCi) IVevery 8 weeks, for a total of 4 doses

• LUTATHERA dosage should be modified based on hematologic,renal, hepatic, or other adverse reactions (see full PrescribingInformation)

− For reduced dose administration instructions, refer to section 2.5(Preparation and Administration) of the full Prescribing Information

Before the infusion

• Somatostatin and its analogs competitively bind somatostatinreceptors and may interfere with the efficacy of LUTATHERA1

− Long-acting SSAs (eg, long-acting octreotide or lanreotide)must be discontinued at least 4 weeks before eachLUTATHERA infusion

− Short-acting SSA (eg, short-acting octreotide injections) mustbe withheld at least 24 hours before each LUTATHERA infusion

• Patients will need screening laboratory tests, typically about2 weeks before each treatment.2 Pregnancy status must be verifiedfor women of child-bearing potential1

On the day of the infusion1

• Before the infusion, patients should receive an antiemetic, and aninfusion of amino acids will be started to help protect the kidneys

• Patients should be advised to hydrate and urinate frequently duringand after administration of LUTATHERA

After the infusion1

• Long-acting octreotide 30 mg intramuscular (IM) is administeredbetween 4 and 24 hours after each LUTATHERA dose. Do notadminister long-acting octreotide within 4 weeks of each subsequentLUTATHERA dose

After the treatment course is complete

• Long-acting octreotide 30 mg IM should continue every 4 weeksuntil disease progression or for up to 18 months after LUTATHERAtreatment initiation1

• Patients should receive periodic imaging, assessment ofsymptoms, and laboratory tests to identify signs of progressionand adverse events2

IMPORTANT SAFETY INFORMATION1

WARNINGS AND PRECAUTIONS (continued) Hepatotoxicity: In ERASMUS, <1% of patients were reported to have hepatic tumor hemorrhage, edema, or necrosis, with one 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 based on severity of hepatic impairment.

Please see additional Important Safety Information throughout and accompanying full Prescribing Information.

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Radiation safety recommendations for patients after LUTATHERA administration2

For the first 3 DAYS, patients should follow these recommendations

• Sleep in a separate bed and avoid intimate contact

• Use the toilet in a seated position, even for men, and usetoilet paper each time

• Flush toilet paper and/or wipes down the toilet

• Close the toilet lid prior to flushing and double-flush thetoilet after each use

• Wash hands every time they use the toilet

• Use separate towels and washcloths

• Use a general guideline of being no closer than 3 feet forno more than 1 hour per day

• Try to maintain a distance of 6 feet from others

• For infants, children, or pregnant women, maintain adistance of 6 feet away for more than 3 days

• Minimize use of public transportation and public facilities

• Return to work when they’re able to be in close proximityto others, depending on how they feel

Patient instructions

These recommendations should be considered as general guidelines only.

Please see additional Important Safety Information throughout and accompanying full Prescribing Information.

IMPORTANT SAFETY INFORMATION1

WARNINGS AND PRECAUTIONS (continued)Neuroendocrine hormonal crisis: Manifesting with flushing, diarrhea, bronchospasm and hypotension, neuroendocrine hormonal crisis occurred in <1% of patients in ERASMUS and typically occurred during or within 24 hours following the initial LUTATHERA dose. 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. 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 3-4 adverse reactions (≥4% with a higher incidence in LUTATHERA arm) observed in NETTER-1 were lymphopenia (44%), increased GGT (20%), vomiting (7%), nausea (5%), elevated AST (5%), increased ALT (4%), hyperglycemia (4%), and hypokalemia (4%). In ERASMUS, the following serious adverse reactions have been observed with a median follow-up time of more than 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. Corticosteroids can induce down-regulation of subtype 2 somatostatin receptors (SSTR2). Avoid repeated administration of high doses of glucocorticosteroids during treatment with LUTATHERA.

SPECIFIC POPULATIONSLactation: 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.To report SUSPECTED ADVERSE REACTIONS, contact Advanced Accelerator Applications USA, Inc. at 1-844-863-1930, or us-pharmacovigilance@adacap.com, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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A targeted therapy that may provide important benefits for your patients with GEP-NETs

• Treatment with LUTATHERA requiresthe collaborative efforts of amultidisciplinary team2

• Your counseling plays an important partin the patient’s treatment journey and canhelp create a positive treatment experience− Find more information and resources

at hcp.lutathera.com

• AAA PatientCONNECT™ provides services tosupport your patient’s access to LUTATHERA treatment− Call 1-844-NETS-AAA or visit www.aaapatientconnect.com

IMPORTANT SAFETY INFORMATION1

WARNINGS AND PRECAUTIONS (continued)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. Please see additional Important Safety Information throughout and accompanying full Prescribing Information.References: 1. LUTATHERA® [prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; May 2020. 2. Hope TA, Abbott A, Colucci K, et al. NANETS/SNMMI procedure standard for somatostatin receptor–based peptide receptor radionuclide therapy with 177Lu-DOTATATE. J Nucl Med. 2019;60(7):937-943. 3. Strosberg J, El-Haddad G, Wolin E,et al, for the NETTER-1 trial investigators. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. 4. Zamora V, Cabanne A, Salanova R, et al. Immunohistochemical expression of somatostatinreceptors in digestive endocrine tumours. Dig Liver Dis. 2010;42(3):220-225. 5. Thundimadathil J. Cancer treatment usingpeptides: current therapies and future prospects. J Amino Acids. 2012;2012:967347:1-13. 6. Olmstead C, Cruz K, Stodilka R,Zabel P, Wolfson R. Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol. Nucl Med Commun. 2015;36(2):129-134. 7. Calais PJ, Turner JH. Radiation safety ofoutpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors. Ann Nucl Med. 2014;28(6):531-539. 8. American Cancer Society. Natural background radiation. www.cancer.org/cancer/cancer-causes/radiation-exposure/x-rays-gamma-rays/natural-background-radiation.html. Accessed January 12, 2019. 9. Friedberg W, Copeland K, Duke FE, O’Brien K III, Darden EB Jr. Radiation exposure during air travel: guidance provided by the Federal Aviation Administration for air carrier crews. Health Phys. 2000;79(5):591-595.

Distributed by: Advanced Accelerator Applications USA, Inc., 57 East Willow Street, Millburn, NJ 07041 LUTATHERA is a registered trademark of Advanced Accelerator Applications SA. © 2020 Advanced Accelerator Applications | All Rights Reserved AAA-Lu177-US-0243 | 07/2020