Lanreotide autogel (LAN) is a long-acting somatostatin analogue used to treat somatostatin receptor-positive (SSTR+), gastroenteropancreatic neuroendocrine tumours (GEP-NETs).1 In the CLARINET study, LAN 120 mg every (q)28 days significantly improved progression-free survival (PFS) versus placebo in patients with metastatic, SSTR+ GEPNETs. CLARINET FORTE is an ongoing phase II study assessing the safety and efficacy (centrally assessed median PFS) of increasing the frequency of LAN 120 mg dosing (q14 days) in patients with progressive pancreatic NETs (panNETs) or midgut NETs.
Eligible patients had well-differentiated, metastatic or locally advanced, unresectable, G1/G2, panNETs or midgut NETs with a proliferation index (Ki-67) ≤20%. Patients had radiological progressive disease within 2 years prior to study inclusion as assessed by central review, while receiving first-line treatment with LAN 120 mg with standard treatment intervals (q28) days for ≥24 weeks. Following a 28-day screening interval, LAN 120 mg was administered q14 days. In total, 99 enrolled patients from 10 countries received treatment.
|panNET (n = 48)||Midgut NET (n = 51)|
|Age, mean (SD)||63.3 (10.6)||67.1 (8.2)|
|Male, n (%)||20 (41.7)||29 (56.9)|
|Tumour grading*, %||-||-|
|Proliferation index Ki-67, mean (SD)||6.2 (4.6)||3.5 (3.8)|
|Proliferation index Ki-67 category, n (%)||-||-|
|≥10%||9 (18.8)||4 (8.0)|
|<10%||39 (81.3)||46 (92.0)|
|≤2%†||11 (28.2)||28 (60.9)|
|2–10%†||28 (71.8)||18 (39.1)|
|Hepatic tumour load, n (%) >25% ≤25% Missing||- 6 (13.3) 39 (86.7) 3||- 9 (17.6) 42 (82.4) 0|
|Previous primary tumour surgery||18 (37.5)||12 (23.5)|
|Krenning scale, n (%) Grade 1 Grade 2 Grade 3 Grade 4 N/A‡ Missing||- 0 6 (12.5) 10 (20.8) 28 (58.3) 4 (8.3) 0||- 4 (8.5) 4 (8.5) 15 (31.9) 21 (44.7) 3 (6.4) 4|
|Duration of LAN treatment (standard dosing interval) prior to study enrolment in months, median (range)||21.7 (5–103)||16.4 (5–198)|
|Diarrhoea presence, % Flushing presence, %||16.7 8.3||41.7 28.0|
Percentages are based on the number of subjects with a Ki-67 <10 %.‡
Patients who had a PET scan with gallium.
Baseline CLARINET FORTE data highlight the high rate of G1 in progressive midgut NET and of G2 in panNET. The cohort is representative of typical patients requiring treatment intensification due to progressive panNET or midgut NET. Final analyses are expected in Q1 2020, which will provide efficacy and safety data on use of LAN 120 mg at an increased dosing frequency. 1. Somatuline autogel SmPC. November 2018.
Clinical trial identification
Editorial assistance was provided by Louise Cully of Ashfield Healthcare and funded by Ipsen.
Legal entity responsible for the study
P. Ruszniewski: Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: AAA; Advisory / Consultancy: Keocyt. J. Ćwikła: Advisory / Consultancy, PI in Poland for this study: Ipsen. C. Lombard-Bohas: Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self): Pfizer ; Advisory / Consultancy, Research grant / Funding (self): Novartis. I. Borbath: Advisory / Consultancy: Pfizer ; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Celgene. T. Shah: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen. U. Pape: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self): Novartis. X. Truong Thanh: Full / Part-time employment: Ipsen. A. Houchard: Full / Part-time employment: Ipsen. M.E. Pavel: Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Lexicon.