Progression-free survival (PFS) with lanreotide autogel/depot (LAN) in enteropancreatic NETs patients: The CLARINET extension study.

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Abstract
4107^ Background: The CLARINET core study showed that the long-acting somatostatin analog (SSA) LAN 120 mg significantly prolonged PFS vs placebo (PBO) in patients (pts) with metastatic enteropancreatic NETs (p=0.0002). Median PFS not reached with LAN vs 18.0 months with PBO. This study was the first randomized PBO-controlled trial investigating PFS with an SSA in a population that included pts with pancreatic NETs and pts with grade G2 tumors (Ki-67 <10%). Here, we report PFS data and safety findings from the open-label extension (OLE) to CLARINET. Methods: Pts enrolled in CLARINEThad: well/moderately differentiated non-functioning enteropancreatic NETs with Ki-67 <10%; no prior SSAs, or other medical therapies in last 6 months; metastatic disease. In CLARINET, pts were randomized to LAN 120 mg (n=101) or PBO (n=103) every 28 days for 96 wks or until death/disease progression (PD; according to RECIST 1.0). LAN pts with stable disease and PBO pts with/without PD could then enter the single-arm (LAN) OLE (NCT00842348, max. expected duration 5 yrs). The primary objective of the OLE was safety (safety population). The main efficacy endpoint was PFS (i.e. time from randomization in core study to death/PD) for the core study intent-to-treat population, using survival analysis based on Kaplan–Meier estimates. Results: 88 pts from the CLARINET core study (LAN arm, 41; PBO arm, 47) participated in OLE. At core study enrollment, 96% of OLE patients did not have tumor progression; 38% had pancreatic primary tumors, 39% had midgut, and 8% hindgut. The median PFS for LAN was reached during the OLE: 32.8 months. For subset of pts who had PD while on PBO in the core study, median time to further PD with LAN in the OLE was 14.0 months. During the OLE, 27% who continued LAN vs 40% switched to LAN had treatment-related adverse events (TRAE); most frequent TRAE was diarrhea. No new safety concerns were identified in the extension. Conclusions: CLARINET extension data suggest there were antitumor effects with LAN 120 mg in enteropancreatic NET patients with progressive disease. Long-term safety/tolerability of lanreotide in the extension was consistent with its known profile. Clinical trial information: NCT00842348.