Peptide education
Lanreotide
Somatuline Depot · Somatuline Autogel · BIM-23014
Lanreotide is a prescription somatostatin analog that suppresses growth hormone and other secretions. In the United States, Somatuline Depot is a long-acting formulation given by deep subcutaneous injection. Its label covers specified acromegaly, neuroendocrine tumor and carcinoid-syndrome settings.
In CLARINET, a trial of 204 patients with selected advanced nonfunctioning neuroendocrine tumors, median progression-free survival was not reached with lanreotide and was 18.0 months with placebo. The study did not establish an overall survival advantage.
Overview
Quick answer
Slowing tumor progression, controlling hormone levels and reducing rescue medication use are different treatment goals. Lanreotide has evidence for each in specific populations, but a positive result for one endpoint does not prove benefit for every neuroendocrine tumor or symptom.
What is lanreotide used for?
The US label covers long-term treatment of acromegaly when surgery or radiotherapy has not worked adequately or is not an option. It also covers defined unresectable, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors in adults, and adult carcinoid syndrome to reduce the need for short-acting rescue therapy.
What did the tumor study measure?
CLARINET measured progression-free survival, the time until tumor progression or death. Participants had advanced nonfunctioning, receptor-positive, well or moderately differentiated tumors. Median progression-free survival was not reached on lanreotide versus 18.0 months on placebo.
How is Somatuline Depot given?
The US product is intended for deep subcutaneous injection by a healthcare provider. Label doses differ by indication: the usual acromegaly starting schedule is 90 mg every 4 weeks for 3 months, while the GEP tumor and carcinoid-syndrome schedules are 120 mg every 4 weeks.
What safety issues matter?
The label warns about gallstones and complications, high or low blood glucose, decreased heart rate, thyroid changes, hypersensitivity and fat malabsorption. The monitoring plan and dose depend on the clinical setting.
Evidence
Evidence snapshot
Somatuline Depot is labeled for specified acromegaly care, selected advanced GEP neuroendocrine tumors to improve progression-free survival, and adult carcinoid syndrome to reduce short-acting rescue therapy.
In 204 randomized patients, median progression-free survival was not reached with lanreotide and was 18.0 months with placebo. The hazard ratio for progression or death was 0.47. The US label reports a placebo median of 16.6 months for the same study.
In a 115-person carcinoid-syndrome trial, the adjusted mean percentage of days using rescue octreotide was 33.7% with lanreotide and 48.5% with placebo.
A randomized study measured reductions in growth hormone after an initial depot injection, then followed patients through active treatment. The placebo-controlled period was short.
Gallstones, glucose changes, reduced heart rate, thyroid changes and fat malabsorption appear in the prescribing information.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Lanreotide can delay progression in certain neuroendocrine tumors. | CLARINET compared lanreotide depot with placebo in advanced nonfunctioning, receptor-positive tumors of the pancreas, intestine or unknown origin. The primary endpoint was progression-free survival, not tumor cure. | Lanreotide binds somatostatin receptors, particularly subtypes 2 and 5, but receptor binding alone does not predict an individual patient's outcome. | Supported in the studied population. The US label specifies adult patients with unresectable, well or moderately differentiated, locally advanced or metastatic GEP neuroendocrine tumors. |
| A longer progression-free interval proves longer overall survival. | CLARINET reported a longer progression-free interval with lanreotide but did not find a significant difference in overall survival between groups. | Not established by this trial. Progression-free survival and overall survival are separate outcomes. | |
| Lanreotide can reduce rescue treatment use in carcinoid syndrome. | ELECT randomized 115 patients and allowed rescue short-acting octreotide in both groups. The lanreotide group used rescue medication on a smaller percentage of days over the 16-week study. | Supported for the trial's rescue-use endpoint and reflected in the adult carcinoid-syndrome label. It is not the same endpoint as tumor progression. | |
| A similar name guarantees an equivalent compounded depot. | The studies and label concern a specific prolonged-release formulation. FDA states that compounded drugs are not approved and are not checked by FDA for safety, effectiveness or quality before marketing. | No. Identity, concentration, release profile and quality require separate product-specific evidence. |
Bottom line
Main takeaway
Lanreotide is a prescription medicine for certain endocrine disorders and neuroendocrine tumors. The depot is given as a deep injection under the skin.
Keep three goals apart: lowering growth hormone and IGF-1 in acromegaly, delaying progression of defined GEP tumors, and reducing rescue medication use in carcinoid syndrome.
CLARINET studied receptor-positive, nonfunctioning grade 1 or 2 tumors with Ki-67 below 10%; 96% had no progression documented in the preceding 3 to 6 months. ELECT used rescue medication days as a different endpoint.
Identity
What it is
Lanreotide is an eight-residue cyclic analog of somatostatin. The US depot contains a prolonged-release formulation in a prefilled syringe, intended for deep subcutaneous administration by a healthcare provider.
Its binding to somatostatin receptors contributes to suppression of growth hormone and other secretions. In acromegaly, clinicians use growth hormone and IGF-1 measurements to assess treatment response.
Neuroendocrine tumor treatment has more than one goal. CLARINET studied time to progression or death in selected nonfunctioning tumors, while ELECT measured use of rescue octreotide among patients with carcinoid syndrome.
Use context
Routes, doses, and cycle patterns
Somatuline Depot is given by deep subcutaneous injection. The labeled acromegaly starting dose differs from the doses for adult GEP tumors and carcinoid syndrome.
Human studies and product labels
Somatuline Depot for acromegaly
- Purpose
- Long-term biochemical and symptom control in the labeled setting
- Context
- US prescribing information
- Route
- Deep subcutaneous injection by a healthcare provider
- Amount
- 90 mg initially
- Frequency
- Every 4 weeks
- Duration
- Initial 3 months, followed by response-based adjustment
The label describes a 60 mg starting dose for acromegaly with moderate or severe renal or hepatic impairment. Later adjustments depend on hormone levels and symptoms.
Somatuline Depot for advanced GEP neuroendocrine tumors
- Purpose
- Improve progression-free survival in the label-defined adult population
- Context
- US prescribing information
- Route
- Deep subcutaneous injection by a healthcare provider
- Amount
- 120 mg
- Frequency
- Every 4 weeks
- Duration
- According to clinical treatment plan
The indication is limited to unresectable, well or moderately differentiated, locally advanced or metastatic GEP tumors. The label says patients with GEP tumors and severe renal impairment were not studied, nor were patients with hepatic impairment studied for this use.
Somatuline Depot for carcinoid syndrome
- Purpose
- Reduce the frequency of short-acting somatostatin analog rescue therapy
- Context
- US prescribing information
- Route
- Deep subcutaneous injection by a healthcare provider
- Amount
- 120 mg
- Frequency
- Every 4 weeks
- Duration
- According to clinical treatment plan
The label says not to give an additional dose for carcinoid syndrome when a patient is already receiving Somatuline Depot for a GEP tumor.
CLARINET trial regimen
- Purpose
- Progression-free survival in advanced nonfunctioning neuroendocrine tumors
- Context
- Randomized placebo-controlled study
- Route
- Deep subcutaneous prolonged-release depot
- Amount
- 120 mg lanreotide
- Frequency
- Every 28 days
- Duration
- Up to 96 weeks in the randomized study
The result concerns the study's selected population and is not a promise of tumor shrinkage, cure or longer overall survival.
ELECT trial regimen
- Purpose
- Carcinoid-syndrome rescue medication use
- Context
- Randomized placebo-controlled study
- Route
- Deep subcutaneous prolonged-release depot
- Amount
- 120 mg lanreotide
- Frequency
- Every 4 weeks
- Duration
- 16 weeks in the randomized study
Short-acting octreotide was available as rescue treatment to both groups. The primary endpoint counted the percentage of days it was used.
What varies
- Indication: acromegaly, GEP tumor progression and carcinoid syndrome have different treatment goals and label criteria.
- Route: the US depot is administered deeply under the skin by a healthcare provider; product and dose should not be assumed interchangeable with other formulations.
- Monitoring: hormone levels, glucose, gallbladder concerns, heart rate and possible fat malabsorption are relevant to the label.
Research
Research evidence
Lanreotide's evidence depends on the condition and outcome. CLARINET found longer progression-free survival in selected advanced nonfunctioning tumors. ELECT found fewer rescue-medication days in carcinoid syndrome. An acromegaly study measured hormone reductions after an initial randomized comparison, with later active-treatment follow-up.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Somatuline Depot prescribing information | Patients meeting the indication-specific US label criteria | US prescribing information and clinical-study summaries | Deep subcutaneous prolonged-release depot | The label defines the three indications, product-specific doses, administration setting, monitoring and safety warnings. | The GEP tumor indication is restricted by stage, resectability, differentiation and adult age. It does not cover every tumor or every health goal. | Strong for labeled use |
| CLARINET | 204 patients with advanced nonfunctioning receptor-positive grade 1 or 2 tumors | Randomized double-blind placebo-controlled trial over 96 weeks | Lanreotide depot 120 mg or placebo every 28 days | Median progression-free survival was not reached with lanreotide versus 18.0 months with placebo; the hazard ratio for progression or death was 0.47. | Ki-67 was below 10%, and 96% had no documented progression in the preceding 3 to 6 months. The study did not find a significant overall survival difference. The US label reports a 16.6-month placebo median rather than the publication's 18.0 months. | Randomized, population-specific |
| ELECT | 115 patients with carcinoid syndrome and neuroendocrine tumors | Randomized double-blind placebo-controlled trial over 16 weeks | Lanreotide depot or placebo with rescue octreotide available | Adjusted mean days with rescue use were 33.7% in the lanreotide group and 48.5% in the placebo group. | Rescue use was a patient-reported measure in a short trial. It does not establish tumor shrinkage or a survival advantage. | Randomized, symptom-management endpoint |
| Acromegaly hormone-response study | 108 enrolled patients with acromegaly | Short randomized placebo-controlled phase followed by active treatment through 52 weeks | Lanreotide Autogel prolonged-release injection | Four weeks after the first injection, 63% on lanreotide and 0% on placebo had a greater than 50% reduction in growth hormone from baseline. | The placebo comparison was short, and later results were not from a year-long placebo-controlled comparison. Hormone reduction is not identical to normal hormone levels in every patient. | Randomized early response, open follow-up |
Use context
Reported use context
CLARINET studied progression-free survival in advanced nonfunctioning tumors. ELECT measured rescue octreotide use in patients with carcinoid syndrome.
Study and label context
120 mg every 28 days, compared with placebo for up to 96 weeks.
Patients had advanced nonfunctioning neuroendocrine tumors.120 mg every 4 weeks for 16 weeks, with rescue octreotide available in both groups.
The primary endpoint was the percentage of days with rescue use.Cautions
Safety and unknowns
- Lanreotide can reduce gallbladder motility and cause gallstones. The label describes complications including gallbladder inflammation, cholangitis and pancreatitis, and recommends periodic monitoring.
- Blood glucose can rise or fall. The label recommends glucose monitoring when treatment starts or the dose changes, with diabetes-treatment adjustment when appropriate.
- Decreased heart rate and thyroid function changes can occur. The label calls for caution in patients with existing cardiac disorders and thyroid testing when clinically indicated.
- New or worsening loose, oily stools, bloating or weight loss can indicate fat malabsorption or pancreatic exocrine insufficiency and warrant clinical review.
- Hypersensitivity, including anaphylaxis and angioedema, has been reported. The product is contraindicated for patients with a history of hypersensitivity to lanreotide.
- The label says GEP tumor patients with severe renal impairment were not studied. It also says Somatuline Depot was not studied in patients with hepatic impairment for GEP tumors.
- The label says it is not known whether lanreotide passes into human milk and advises against breastfeeding during treatment and for 6 months after the last dose. Pediatric safety and effectiveness have not been established.
Product quality
Product identity and quality
Somatuline Depot is a prolonged-release preparation in a single-dose prefilled syringe. Its dose and injection route belong to that product.
FDA states that compounded drugs are not FDA-approved and are not assessed by FDA for safety, effectiveness or quality before marketing.
Depot formulation
The clinical evidence describes a specific prolonged-release product and route.
Identity and quality
A name alone cannot establish the identity, concentration or quality of another preparation.
Mechanism
How it is proposed to work
Lanreotide acts like somatostatin, binding to receptors involved in regulating hormone release. It can lower growth hormone and IGF-1 and affect other endocrine and digestive secretions.
The label describes high affinity for somatostatin receptor subtypes 2 and 5, with activity at these receptors thought to contribute to growth-hormone suppression.
Inhibition of insulin and glucagon secretion can contribute to changes in blood glucose. Reduced gallbladder motility is relevant to gallstone risk.
Details
Technical details
Sources
References
- 1.
DailyMed. Somatuline Depot prescribing information
US prescribing information for lanreotide depot, including indications, deep subcutaneous administration, dosing and precautions.
- 2.
PubMed. Lanreotide in metastatic enteropancreatic neuroendocrine tumors: CLARINET
doi:10.1056/NEJMoa1316158 PMID:25014687 NCT00353496
Randomized placebo-controlled trial of lanreotide depot in advanced nonfunctioning enteropancreatic neuroendocrine tumors.
- 3.
PubMed. Lanreotide depot for carcinoid syndrome: the ELECT randomized trial
doi:10.4158/EP151172.OR PMID:27214300 NCT00774930
Randomized trial comparing rescue octreotide use in patients with carcinoid syndrome receiving lanreotide or placebo.
- 4.
PubMed. Lanreotide Autogel in acromegaly: randomized placebo-controlled study with an open extension
PMID:19639415
Acromegaly study with a short placebo-controlled phase followed by active-treatment phases through 52 weeks.
- 5.
FDA. Compounding and the FDA: Questions and Answers
FDA explains that compounded drugs are not approved and are not evaluated by FDA before marketing for safety, effectiveness or quality.