Effects of lanreotide autogel/depot (LAN) in pancreatic neuroendocrine tumors (pNETs): A subgroup analysis from the CLARINET study.

233 Background: The prognosis for patients with metastatic pNETs is generally poor and current treatment options can be complicated by safety considerations. In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 <10%) non-functioning enteropancreatic NETs (hazard ratio [HR] for progressive disease [PD]/death: 0.47 [95% CI: 0.30, 0.73]. Here, we more fully characterize treatment effects in the pNET subgroup. Methods: CLARINET was a 96-week randomized double-blind trial. Patients received LAN 120 mg or PBO every 4 weeks, administered by deep s.c. injection (NCT00353496). Subgroup analyses were undertaken to investigate only the consistency of treatment effects as the study was not otherwise designed or powered for such analyses. Results: 91 patients with pNETs received LAN (n=42) or PBO (n=49). At baseline, mean age was 64 years in both groups; overall, 37% had hepatic tumor loads >25%, 95% had stable disease, 77% had received no previous treatment, and 38% had had previous surgery on the tumor. Median PFS in the pNET subgroup was not reached at study end with LAN vs. 12.1 months [95% CI: 9.4, 18.3] with PBO (HR for PD/death: 0.58 [0.32, 1.04]). (Median PFS for LAN at first planned analysis in the open-label extension study was 29.7 months [12.0, 32.4].) The incidence of adverse events (AEs) in the core study was 88% with both LAN and PBO, and the most common AE was diarrhea (LAN, 43%; PBO, 37%). Treatment-related AEs occurred in 55% of the LAN group and 24% of the PBO group. Serious AEs (SAEs) occurred in 29% vs. 43%, respectively; only three of these patients had treatment-related SAEs (two with LAN, one with PBO). Two patients in each group had AEs leading to withdrawal. Conclusions: The evidence in the pNET subgroup suggesting antitumor effects with LAN together with the favorable long-term safety profile support a positive benefit:risk profile for LAN as a first-line treatment for pNETs. Clinical trial information: NCT00353496.