Abstract 3975
Background
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.
Methods
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.
Results
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) |
| Treatment-related | NA | 0 | 0 | NA | 1 (2) |
NA, not applicable (no patients withdrawn from core study were entered into OLE study).
Conclusions
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
2-55-52030-729
Legal entity responsible for the study
N/A
Funding
Ipsen
Disclosure
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.