LUTATHERA® (lutetium [177Lu] oxodotreotide) Safety Information
LUTATHERA® has a well understood safety profile1
The overall safety profile is based on pooled data from clinical trials (NETTER-1 pivotal Phase III and ERASMUS long-term Phase I/II), and compassionate use programmes.
The most common adverse events observed were nausea (58.9%) and vomiting (45.5%).1
- The causality of nausea and vomiting is confounded by the emetic effect of the concomitant amino acid infusion administered for renal protection
- In NETTER-1, most cases of nausea and vomiting were low grade, and resolved once the amino acid infusions were completed2
Due to the bone marrow toxicity of LUTATHERA®, the most expected adverse reactions were related to haematological toxicity:1
- Thrombocytopenia (25%)
- Lymphopenia (22.3%)
- Anaemia (13.4%)
- Pancytopenia (10.2%)
Other very common adverse reactions reported include:1
- Fatigue (27.7%)
- Decreased appetite (13.4%)
Adverse events in NETTER-1
As of the final analysis, 76% (84/111) of patients in the LUTATHERA® arms received all four LUTATHERA® infusions, with only 11% of patients discontinuing treatment due to adverse events.*3
The majority of grade 3/4 adverse reactions were comparable between the LUTATHERA® group and active control group.2
- The most common grade 3/4 adverse reactions were vomiting, nausea, diarrhoea, abdominal pain, and lymphopenia, which occurred in 9% or less of patients taking LUTATHERA® plus octreotide LAR 30 mg
- More patients experienced grade 3 or 4 haematologic events in the LUTATHERA® groups vs the control group; however, these events were transient
*Cut-off date 18 January 2021. Safety population n=231.
NETTER-1 Adverse events table (safety population)
| EVENT | 177Lu-dotatate group (N=111) |
Control group (N=110) |
P value† | ||
| Any grade | Grade 3 or 4 | Any grade | Grade 3 or 4 | Any grade | |
| No. of patients (%) | |||||
| Any adverse event | 105 (95) | 46 (41) | 92 (84) | 36 (33) | 0.01 |
| Gastrointestinal disorders | |||||
| Nausea | 65 (59) | 4 (4) | 13 (12) | 2 (2) | <0.001 |
| Vomiting | 52 (47) | 8 (7) | 11 (10) | 1 (1) | <0.001 |
| Abdominal pain | 29 (26) | 3 (3) | 29 (26) | 6 (5) | 1.00 |
| Diarrhoea | 32 (29) | 3 (3) | 21 (19) | 2 (2) | 0.11 |
| Distension | 14 (13) | 0 | 15 (14) | 0 | 0.84 |
| General disorders | |||||
| Fatigue or asthenia | 44 (40) | 2 (2) | 28 (25) | 2 (2) | 0.03 |
| Oedema peripheral | 16 (14) | 0 | 8 (7) | 0 | 0.13 |
| Blood disorders | |||||
| Thrombocytopenia | 28 (25) | 2 (2) | 1 (1) | 0 | <0.001 |
| Anaemia | 16 (14) | 0 | 6 (5) | 0 | 0.04 |
| Lymphopenia | 20 (18) | 10 (9) | 2 (2) | 0 | <0.001 |
| Leukopenia | 11 (10) | 1 (1) | 1 (1) | 0 | 0.005 |
| Neutropenia | 6 (5) | 1 (1) | 1 (1) | 0 | 0.12 |
| Musculoskeletal disorders | |||||
| Musculoskeletal pain | 32 (29) | 2 (2) | 22 (20) | 1 (1) | 0.16 |
| Nutrition disorders | |||||
| Decreased appetite | 20 (18) | 0 | 9 (8) | 3 (3) | 0.04 |
| Nervous system disorders | |||||
| Headache | 18 (16) | 0 | 5 (5) | 0 | 0.007 |
| Dizziness | 12 (11) | 0 | 6 (5) | 0 | 0.22 |
| Vascular disorders | |||||
| Flushing | 14 (13) | 1 (1) | 10 (9) | 0 | 0.52 |
| Skin disorders | |||||
| Alopecia | 12 (11) | 0 | 2 (2) | 0 | 0.01 |
| Respiratory disorders | |||||
| Cough | 12 (11) | 0 | 6 (5) | 0 | 0.22 |
Adapted from Strosberg et al, 2017.
†Reported are all common adverse events for the LUTATHERA® group (>10%), with the exception of neutropenia (which was reported in <10% of patients).2
LUTATHERA®’s long-term safety profile
At the time of the NETTER-1 final analysis, after a median follow-up time of over 6 years for each study arm, the safety profile remained consistent with that previously reported at 24 months follow-up, with no new safety signals identified.3
A total of 2/111 (2%) of the LUTATHERA®-treated patients developed myelodysplastic syndrome (MDS), with no new cases reported in the long-term follow-up period.3
No cases of acute myeloid leukaemia were reported throughout the entire study,3 although cases have been observed after treatment with LUTATHERA®.1
LUTATHERA® treatment was not associated with any long-term detrimental impact on kidney function;3 however, renal toxicity is a common adverse event and special warning associated with LUTATHERA® use.1
Managing adverse reactions¹
Management of severe or intolerable adverse drug reactions may require temporary dose interruption (extension of the dosing interval from 8 weeks up to 16 weeks), dose reduction, or permanent discontinuation of treatment with LUTATHERA®. See Table 3 from the LUTATHERA® SmPC for the full recommended dose modifications.
Please see the summary of product characteristics for full safety information.
References
- LUTATHERA® Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/12723/smpc#gref [Accessed January 2024].
- Strosberg J, et al. N Engl J Med 2017; 376(2):125–135.
- Strosberg J, et al. Lancet Oncol 2021; 22(12):1752–1763.
