The CLARINET core study established the antitumour activity of lanreotide Autogel 120mg/28 days (LAN) in metastatic enteropancreatic neuroendocrine tumours (NETs). The vast majority of the core study population (96%) had stable disease (SD) at baseline, but the LAN open-label extension (OLE) also included patients with progressive disease (PD; while receiving placebo [PBO] in the core study). Here, we report the final analysis of time to subsequent death/PD for patients with PD switched to LAN.
In the core study, patients with metastatic well-/moderately differentiated non-functioning enteropancreatic NETs received LAN/PBO for 96 weeks or until death/PD (RECIST 1.0). Eligible patients for the OLE (NCT00842348) had SD at core-study end or PD (with PBO only) during the core study. Adverse events (AEs) were recorded at 4-weekly visits. CT/MRI scans from OLE baseline (week 1) and every 24 weeks subsequently were assessed locally for PD (RECIST 1.0). Primary objective: long-term safety. Secondary objective: long-term efficacy, with assessments including PFS and time to subsequent death/PD (from Kaplan–Meier analyses; months approximated as 4 weeks).
89 patients were treated in both core and OLE studies (42 LAN–LAN [SD, n = 41]; 47 PBO–LAN [SD, n = 15]); 40% of the LAN–LAN vs. 47% of the PBO–LAN group had treatment-related AEs. Overall median LAN PFS, based on the intent-to-treat population (n = 101), was 38.5 months. Seven PD events (no deaths) occurred during the OLE in 15 patients entering with SD from the PBO arm of core study. In total, 32 patients with PD whilst receiving PBO in the core study entered OLE (of 59 potentially eligible); NETs were in pancreas in 17 patients, midgut in 10, hindgut in one, and of other/unknown origin in four. Of these patients, 20 had subsequent PD during the OLE and three died; median time to subsequent death/PD was 19.0 months [95% CI: 10.1; 26.7].
The final analysis of the CLARINET OLE study suggests benefit with LAN in patients who had experienced PD when receiving no NET-specific treatment (PBO), with median time to subsequent death/PD of 19 months.
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J.B. Cwikla: Travel expenses paid by Ipsen. E.M. Wolin: Advisory boards for Ipsen and Advanced Accelerator Applications. M. Pavel: Advisory boards and honoraria from Ipsen, Novartis, Pfizer and Lexicon; funding from Ipsen and Novartis for scientific research. A.T. Phan: Consultant for Ipsen and Novartis; Speaker’s bureau for Lilly, Genentech, Celgene, Lexicon, Novartis and Ipsen. M. Raderer: Honoraria from Ipsen, Novartis, Celgene, Roche and EASAI. E. Sedláčková: Consultant role for Ipsen; Speaker’s bureau for Ipsen, Novartis and Merck; funding from Ipsen and Novartis for scientific research; travel expenses paid by Ipsen, Novartis, Roche and Merck. G. Cadiot: Consultant role for Ipsen, Novartis, Advanced Accelerator Applications, and Keocyt; funding from Ipsen and Novartis for scientific research. J. Capdevila: Research, advisory role and speaker for Ipsen, Pfizer and Novartis. G. Rindi: Speaker’s bureau for Ipsen and Novartis. C. Lombard-Bohas: Consultant role for Ipsen, Pfizer and Novartis; funding from Ipsen and Novartis for scientific research. N. Liyanage, X-M. Truong Thanh: Employee of Ipsen P. Ruszniewski: Honoraria from Ipsen and Novartis; consultant role for Ipsen; Speaker’s bureau for Ipsen and Novartis; funding from Ipsen and Novartis for scientific research. M. Caplin: Honoraria from, consulted for, and participated in Speaker’s bureau for Ipsen and Novartis.