Safety and Tolerability Profile of LUTATHERA® (lutetium Lu 177 dotatate)
Radiation safety: general precautions for radiopharmaceuticals
LUTATHERA is a radiopharmaceutical. Radiopharmaceuticals, including LUTATHERA, should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
Minimize radiation exposure during and after treatment with LUTATHERA consistent with institutional good radiation safety practices and patient management procedures. Always follow the principal of ALARA (as low as reasonably achievable) when handling and administering LUTATHERA. Use waterproof gloves and effective radiation shielding when handling LUTATHERA.
The most common Grade 3-4 adverse reactions ≥ 4% with a higher incidence in LUTATHERA arm were:
- Lymphopenia (44%)
- Increased GGT (20%)
- Vomiting (7%)
- Nausea (5%)
- Elevated AST (5%)
- Increased ALT (4%)
- Hyperglycemia (4%)
- Hypokalemia (4%)
6% of patients required a dose reduction, and 13% of patients discontinued LUTATHERA.
- 5 patients discontinued due to renal-related events
- 4 patients discontinued due to hematological toxicities
*National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Only displays adverse reactions occurring at a higher incidence in LUTATHERA-treated patients [between arm difference of ≥5% (all grades) or ≥2% (grades 3-4)].
†Includes the terms: Glomerular filtration rate decreased, acute kidney injury, acute prerenal failure, azotemia, renal disorder, renal failure, renal impairment.
‡Includes the terms: Dysuria, micturition urgency, nocturia, pollakiuria, renal colic, renal pain, urinary tract pain, and urinary incontinence.
*Values are worst grade observed after randomization.
†National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Only displays laboratory abnormalities occurring at a higher incidence in LUTATHERA-treated patients (between arm difference of ≥5% [all grades] or ≥2% [grades 3-4]).
Serious adverse reactions reported with a median follow-up time of more than 4 years1,2
Retrospective safety data are available from 1,214 patients in ERASMUS, an international, single-institution, single-arm, open-label trial of patients with somatostatin receptor-positive tumors (neuroendocrine and other primaries). Patients received LUTATHERA 7.4 GBq (200 mCi) administered every 6 to 13 weeks for up to 4 doses with the recommended amino acid solution and antiemetic. Retrospective medical record review was conducted on a subset of 811 patients to document serious adverse reactions. 81% of patients in the subset received a cumulative dose ≥22.2 GBq (≥600 mCi).
5-HIAA, 5-hydroxyindoleacetic acid; ALT, alanine aminotransferase; CrCl, creatinine clearance; AST, aspartate aminotransferase; ENETS, European Neuroendocrine Tumor Society; GGT, gamma-glutamyl transferase; IM, intramuscular; IV, intravenous; RECIST, Response Evaluation Criteria in Solid Tumors; ULN, upper limit of normal.
References: 1. LUTATHERA® [prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; July 2018. 2. Brabander T, van der Zwan WA, Teunissen JJ, et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3] octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res. 2017;23(16):4617-4624.
IMPORTANT SAFETY INFORMATION1
WARNINGS AND PRECAUTIONS
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.
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.
To report SUSPECTED ADVERSE REACTIONS, contact Advanced Accelerator Applications USA, Inc. at 1-844-863-19301-844-863-1930, or firstname.lastname@example.org, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information.
Distributed by: Advanced Accelerator Applications USA, Inc., NJ 07041
References: 1. LUTATHERA® [prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; July 2018.