Relative risk of adverse events with lanreotide depot/autogel (LAN) vs. placebo (PBO) in patients with intestinal and pancreatic neuroendocrine tumors (NETs).

Background: CLARINET was a large 96-week phase 3 study showing that LAN 120 mg significantly improved progression-free survival vs PBO in patients with intestinal and pancreatic NETs. Here, we analyze the safety/tolerability data in greater detail, quantifying the relative risk (RR) of adverse events (AEs). Methods: Patients withmetastatic grade 1/2 (Ki-67 <10%) non-functioning intestinal and pancreatic NETs received LAN 120 mg (n=101) or PBO (n=103) for 96 weeks or until death/disease progression (NCT00353496). TheRR (LAN vs PBO) and 95% CIs were calculated post hoc for any AE occurring in ≥5% of patients in either group. Results: The incidence of AEs overall was similar for LAN and PBO (88% vs 90%). Gastrointestinal disorders were the most common AE class (67% vs 63%; RR 1.1 [0.9, 1.3]) and diarrhea the most common individual AE (35% vs 35%; RR 1.0 [0.7, 1.4]); based on RR, these incidences were not significantly different for LAN vs PBO (lower CIs were ≤1). Furthermore, there were no significant differences for any AE occurring in ≥5% in either group (see Table for the subset occurring in ≥10% in either group), although CIs for RRs were wide in a number of cases.Conclusions: There were no significant safety signals for LAN in the CLARINET study, highlighting its favorable benefit–risk profile in patients with intestinal and pancreatic NETs. For significant difference between treatment groups, lower CIs would need to be >1. Clinical trial information: NCT00353496