Study Results Published in
The New England Journal of Medicine

A landmark registrational trial for tumor control in GEP-NETs

In adult patients with unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

CLARINET: A Phase III, 96-week, international, randomized, double-blind, placebo-controlled trial1-3

CLARINET = Controlled Study of Lanreotide Antiproliferative Response In NeuroEndocrine Tumors.

Secondary endpoints included: Safety, percentage of patients alive and progression-free at Weeks 48 and 96, impact on tumor biomarkers (chromogranin A [CGA] and 5-hydroxyindoleacetic acid [5-HIAA]), quality of life (QoL).

  • Somatuline Depot was administered every 28 days by deep subcutaneous injection
    • Follow-up visits occurred at Weeks 12, 24, 36, 48, 72, and 96

CLARINET enrolled patients with and without prior treatment1,2

  • The majority (84%) of patients in CLARINET had not received prior pharmacologic therapy for GEP-NETs. Some patients (16%) received prior therapy2
  • Patients were excluded if they received:
    • Somatostatin analog at any time, unless they received it >6 months prior to study entry and for <15 days2,3
    • Interferon, chemoembolization, or chemotherapy: <6 months prior to study entry2,3
    • Unlicensed drugs: <30 days prior to study entry3

Studied in a broad range of patient types with varied primary tumor locations and levels of visceral disease burden

  • CLARINET included patients with unresectable, well- to moderately differentiated, locally advanced or metastatic GEP-NETs, a range of hepatic tumor loads, and varying primary tumor locations (foregut/pancreas, midgut, or hindgut)1
  • This population mirrors data showing that in clinical practice, approximately 60% to 80% of all GEP-NETs are diagnosed at the metastatic stage4
  • For the majority of patients enrolled in the pivotal trial, Somatuline Depot was their first-line treatment for GEP-NETs2
Somatuline Depot 120 mg
(n=101)
Placebo
(n=103)
Age (years) 63.3 (30-83) 62.2 (31-92)
Sex
Male
Female

52.5%
47.5%

52.4%
47.6%
Race
Asian
Black/African American
Caucasian/White

2%
2%
96%

5%
2%
93%
Prior medication for NET
Yes
No

16%
84%

16%
84%
Previous chemotherapy for NET
Yes
No

14%
86%

15%
85%
Previous surgery of
the primary tumor*

Yes
No


40%
60%


38%
62%
CgA
≤1 x ULN
>1-2 x ULN
>2 x ULN
Unknown

33 (32.7)
25 (24.8)
41 (40.6)
2 (2)

34 (33)
18 (17.5)
48 (46.6)
3 (2.9)
  • ULN=upper limit of normal.
  • *Patients with prior surgery were allowed to enter CLARINET if surgery occurred >3 months prior to study entry.
Somatuline Depot 120 mg
(n=101)
Placebo
(n=103)
Foregut (pancreas) 42 (42) 49 (48)
Midgut 33 (33) 40 (39)
Hindgut 11 (11) 3 (3)
Other/unknown 15 (15) 11 (11)
Somatuline Depot 120 mg
(n=101)
Placebo
(n=103)
Grade 1:
Ki67 0%-2%

69 (68)

72 (70)
Grade 2:
Ki67 3%-10%

32 (32)

29 (28)
Data Missing 0 2 (2)
Somatuline Depot 120 mg
(n=101)
Placebo
(n=103)
0% 16 (15.8) 18 (17.5)
>0%-10% 33 (32.7) 40 (38.8)
>10%-25% 13 (12.9) 17 (16.5)
>25%-50% 23 (22.8) 12 (11.7)
>50% 16 (15.8) 16 (15.5)
  • Baseline prognostic characteristics were similar between arms with one exception; there were 39% of patients in the Somatuline Depot arm and 27% of patients in the placebo arm who had hepatic involvement by tumor of >25%1
Indication

Somatuline® Depot (lanreotide) Injection 120 mg is indicated for the treatment of adult patients with unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.

Important Safety Information
Contraindications:

Somatuline Depot is contraindicated in patients with hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide.

Warnings and Precautions:
  • Cholelithiasis and Gallbladder Sludge: Somatuline Depot may reduce gallbladder motility and lead to gallstone formation. Periodic monitoring may be needed.
  • Hypoglycemia or Hyperglycemia: Pharmacological studies show that Somatuline Depot, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Blood glucose levels should be monitored when Somatuline Depot treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly.
  • Cardiac Abnormalities: Somatuline Depot may decrease heart rate. In 81 patients with baseline heart rates of ≥60 beats per minute (bpm) treated with Somatuline Depot in the GEP-NETs clinical trial, the incidence of heart rate <60 bpm was 23% (19/81) with Somatuline Depot vs 16% (15/94) with placebo; 10 patients (12%) had documented heart rates <60 bpm on more than one visit. The incidence of documented episodes of heart rate <50 bpm or bradycardia reported as an adverse event was 1% in each treatment group. Initiate appropriate medical management in patients who develop symptomatic bradycardia. In patients without underlying cardiac disease, Somatuline Depot may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia. In patients suffering from cardiac disorders prior to treatment, sinus bradycardia may occur. Care should be taken when initiating treatment in patients with bradycardia.
  • Drug Interactions: The pharmacological gastrointestinal effects of Somatuline Depot may reduce the intestinal absorption of concomitant drugs. Concomitant administration of Somatuline Depot may decrease the relative bioavailability of cyclosporine and may necessitate the adjustment of cyclosporine dose to maintain therapeutic levels.
Adverse Reactions:

In the GEP-NET pivotal trial, the most common adverse reactions (incidence of >10% and more common than placebo) in patients treated with Somatuline Depot vs placebo were abdominal pain (34% vs 24%), musculoskeletal pain (19% vs 13%), vomiting (19% vs 9%), headache (16% vs 11%), injection site reaction (15% vs 7%), hyperglycemia (14% vs 5%), hypertension (14% vs 5%), and cholelithiasis (14% vs 7%).

You may report suspected adverse reactions to FDA at 1-800-FDA-1088 or to Ipsen Biopharmaceuticals, Inc. at 1-888-980-2889.

Please click here for full Prescribing Information and for full Important Safety Information.

References: 1. Somatuline Depot (lanreotide) Injection [Prescribing Information]. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc; December 2014. 2. Caplin ME, Pavel M, Ćwikła JB, et al, for the CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224-233. 3. Data on file. Basking Ridge, NJ: Ipsen Biopharmaceuticals, 2014. 4. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934-959.