A search of the literature did not find strong evidence to support the use of lanreotide in the treatment of neuroendocrine tumours. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by two phase III, randomised, double-blind, placebo-controlled studies:
The multinational CLARINET study involving 204 patients comparing lanreotide with placebo in patients with advanced, well/moderately differentiated, non-functioning, somatostatin receptor–positive neuroendocrine tumors of grade 1 or 2. Patients were randomly assigned to receive lanreotide at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary endpoint was progression-free survival (PFS).r
The ELECT study investigating the utility of lanreotide in controlling symptoms of carcinoid syndrome in patients with/without prior somatostatin analog use. 115 patients were randomized to receive lanreotide at a dose of 120 mg (59 patients) or placebo (56 patients) every 4 weeks for 16 weeks. The primary endpoint was percentage of days with rescue octreotide use.r
Current guidelines recommend dose optimisation in patients whose symptoms are inadequately controlled whilst on treatment. High-dose treatment with lanreotide (>120 mg/month) has shown to improve treatment outcomes without a significant change in safety and tolerability.r
Source |
Study & year published |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase III trials |
Wolin et al 2017r |
Yes |
Yes |
Antiproliferative |
|
Vinik et al 2016r |
Yes |
Yes |
Symptom control |
|
Caplin et al 2014r |
|
|
Antiproliferative |
Phase II trials |
Martin-Richard et al 2013r |
Yes |
Yes |
Antiproliferative |
|
Ruszniewski et al 2004r |
Yes |
Yes |
Symptom control |
Observational studies |
Kang et al 2019r |
Yes |
No |
Antiproliferative
Lanreotide LAR 90/120 mg q4w
|
|
Ruszniewski et al 2016r |
Yes |
No |
Symptom control
Lanreotide LAR 60-120 mg q4w
|
|
Chadha et al 2009r |
Yes |
No |
Antiproliferative
Octreotide LAR 40-90 mg q4w
|
Guidelines |
Date published/revised |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
ESMO |
Jul 2020 |
Yes |
Yes |
Antiproliferative and symptom control |
NCCN |
V.2 Jul 2020 |
Yes |
No doses stated |
Antiproliferative and symptom control |
BCCA |
Nov 2018 |
Yes |
Yes |
Antiproliferative and symptom control |
ENETS |
Mar 2017 |
Yes |
Yes |
Antiproliferative and symptom control |
CCO |
Dec 2016 |
Yes |
Yes |
Antiproliferative and symptom control |
COSA |
Nov 2014 |
Yes |
Yes |
Antiproliferative and symptom control |
Efficacy
A summary of the evidence supporting the effect of this protocol is below:
Outcome |
Study |
No. of patients |
Control arm |
Effect |
Flushing |
Ruszniewski et al 2004r
|
71 |
- |
1.3 episodes* |
Diarrhoea |
- |
1.1 episodes*
|
5-hydroxyindoleacetic acid |
- |
24%** |
Chromogranin A |
- |
38%** |
Percentage of days with rescue octreotide |
Vinik et al 2016r |
115 |
Placebo |
-14.8%*** (95% CI; -26.8% to 2.8% |
Median PFS |
Wolin et al 2017r |
101 |
- |
38.5 months; 95% CI 30.9 to 59.4 |
Caplin et al 2014r |
204 |
Placebo |
Not reached, HR=0.47; 95% CI 0.30 to 0.73 |
* mean no. of episodes less than baseline
** decrease in median levels
*** absolute percentage difference between lanreotide group vs placebo group
Toxicity
Incidence of adverse events is summarised in the table below.r
Adverse events |
Incidence of event (pooled data from CLARINET and CLARINET OLE)
n=41 (%)
|
Diarrhoea |
36.6 |
Abdominal pain |
31.7 |
Constipation |
22 |
Cholelithiasis |
22 |
Headache |
19.5 |
Nausea |
19.5 |
Vomiting |
19.5 |
Dizziness |
17.1 |
Hypertension |
17.1 |