CLARINET is a landmark study that established the antitumour activity of LAN in patients with metastatic intestinal or pancreatic NETs. Here, we report final long-term safety data from the recently completed OLE.
Patients were eligible to take part in the OLE if they had stable disease (with LAN or placebo [PBO]) at the end of, or progressive disease (PBO group only), during the 96-week double-blind core study. All patients received open-label LAN 120 mg by deep subcutaneous injection every 28 days.
In total, 89 patients were treated over the core and OLE studies (42 continued on LAN in both studies [LAN:LAN group] and 47 switched from placebo in core to LAN in OLE [PBO:LAN group]). The adverse event (AE) profile of LAN treatment during both studies is summarised in the Table. The most common class of AEs on LAN:LAN across both studies was GI events (any AE, 81%; any treatment-related AE [TRAE], 43% ); among these, the most frequent were diarrhoea (any AE, 40%; any TRAE, 31%) and abdominal pain (any AE, 38%; any TRAE, 17%). On PBO:LAN in the OLE study, GI events (any AE/any TRAE) occurred in 66%/36%; with diarrhoea in 32%/26% and abdominal pain in 21%/2%. Only five patients withdrew due to AEs, of which only one was treatment-related. No new safety concerns were identified.
AE profile on LAN during the CLARINET core and OLE studies
|LAN:LAN group (n = 42)||PBO:LAN group (n = 47)|
|Core study LAN||OLE study LAN||Pooled both studies||Core study PBO||OLE study LAN|
|Treatment exposure, weeks (mean [±SD])||96.9 (±1.6)||134.1 (±85.4)||234.7 (±84.9)||67.3 (±28.0)||116.1 (±95.2)|
|Any AE, n (%)||39 (93)||34 (81)||40 (95)||44 (94)||42 (89)|
|Severe||10 (24)||12 (29)||18 (43)||13 (28)||13 (28)|
|Moderate||19 (45)||16 (38)||17 (40)||23 (49)||22 (47)|
|Mild||9 (21)||6 (14)||4 (10)||8 (17)||7 (15)|
|Treatment-related||23 (55)||17 (40)||27 (64)||12 (26)||22 (47)|
|Serious AEs, n (%)||9 (21)||11 (26)||17 (40)||12 (26)||14 (30)|
|Treatment-related||1 (2)||2 (5)||3 (7)||1 (2)||2 (4)|
|Withdrawals due to AEs, n (%)||NA||2 (5)||2 (5)||NA||3 (6)|
NA, not applicable (no patients withdrawn from core study were entered into OLE study).
LAN 120 mg treatment, over a period of up to >4 years, showed favourable safety/tolerability in patients with metastatic intestinal and pancreatic NETs. This supports the positive longer-term benefit–risk profile of LAN as an antitumour treatment, which is consistent with previous experience from shorter-term trials.
Clinical trial identification
Legal entity responsible for the study
M. Caplin: Received consulting/advisory fees from Ipsen.
M. Pavel: Received research funding from Novartis and consulting/advisory fees from Ipsen, Novartis, Pfizer and Lexicon.
J.C. Cwikła: Received research funding from Ipsen.
A. Phan: Received research funding from Ipsen, Novartis, Lexicon, Sanofi and Incyte; consulting/advisory fees from Ipsen and Novartis; and speaker fees from Lilly, Genentech, Celgene, Novartis and Ipsen.
M. Raderer: Received honoraria from Novartis, Ipsen, Roche, Pfizer, Bayer and Celgene, and speaker fees from Novartis, Ipsen, Roche, Pfizer, Bayer and Celgene.
G. Cadiot: Received research funding from Ipsen and consulting/advisory fees fromIpsen, Novartis, Keocyt.
E. Wolin: Received research funding fromIpsen and Novartis; consulting/advisory fees from Ipsen, Novartis, Pfizer and Celgene; and honoraria from Ipsen and Novartis.
J. Capdevila: Received consulting/advisory fees from Ipsen, Novartis, Pfizer.
G. Rindi: Has received speaker fees from Ipsen.
N. Liyanage, S. Braun: Employee of Ipsen.
P. Ruszniewski: Received research funding from Ipsen and Novartis, speaker fees from Ipsen and Novartis, consulting/advisory fees from Ipsen, honoraria from Ipsen and Novartis.
All other authors have declared no conflicts of interest.