Background: Systemic treatment options for advanced NET continue to be limited. In the phase III RADIANT-2 study, everolimus, an oral mTOR inhibitor, plus octreotide LAR provided a clinically meaningful 5.1-month increase in median progression-free survival (PFS) vs placebo plus octreotide LAR (P+O) in pts with advanced, low- or intermediate-grade NET and a history of secretory symptoms associated with carcinoid syndrome (ESMO 2010 Abstract LBA8). We sought to determine the effect of previous treatment with a long-acting somatostatin analog (SSA) on PFS in this trial. Methods: Pts were randomized to everolimus 10 mg/d orally + octreotide LAR 30 mg intramuscularly q28d (E+O; n=216) or P+O (n=213). The primary endpoint was PFS per central review by RECIST (v1.0). SSA treatment before study entry study was permitted. Pts previously administered SSA in each treatment arm were identified. Results: Of 429 pts randomized to treatment, 339 (79%) had received SSA therapy before study entry, including 173 (80%) in the E+O group and 166 (78%) in the P+O group. More pts with prior SSA therapy vs those without had small intestine (85% vs 15%), lung (66% vs 34%), and colon (79% vs 21%) as the primary disease site. Elevated baseline chromogranin A (81% vs 19%) and 5-hydroxyindoleacetic acid (85% vs 15%) levels were also observed in pts with prior SSA therapy vs those without. Pts with prior SSA therapy vs those without had longer time (>6 months) since diagnosis (82% vs 18%). Everolimus improved median PFS vs placebo in pts with and without previous SSA treatment (Table). Conclusions: Treatment with everolimus plus octreotide LAR produces a clinically meaningful prolongation of median PFS benefit irrespective of previous SSA treatment in pts with advanced NET and a history of secretory symptoms associated with carcinoid syndrome.