Background: In the phase III RADIANT-3 trial, everolimus, an oral mTOR inhibitor, demonstrated superiority in progression-free survival (PFS) with a median of 11.0 versus 4.6 mo for placebo (HR=0.35; 95% CI, 0.27-0.45; P<0.0001) in patients with advanced pNET (ESMO 2010, Abstract LBA9). Here we present an exploratory analysis of the impact of long-acting somatostatin analog (SSA) therapy in this trial. Methods: Patients with progressive advanced low- or intermediate-grade pNET were randomized to everolimus 10 mg/d orally (n=207) or placebo (n=203); both arms received best supportive care. Long-acting SSAs were permitted before entry and as best supportive care during the study. The primary endpoint was PFS (RECIST v1.0). Patients who received SSA therapy before and during the study in each treatment arm were identified. Results: Overall, 203 (50%) patients received SSA therapy before study entry, and 163 (40%) received SSA therapy during the study. Of those patients with prior SSA therapy, 145 (71%) also received SSA therapy during the trial. Treatment arms were well balanced with respect to prior SSA treatment (50%, everolimus arm; 50%, placebo arm) and on-study SSA treatment (39%, everolimus arm; 40%, placebo arm). An improvement in median PFS was observed with everolimus compared with placebo in patients who had any SSA (11.4 mo vs 3.9 mo; HR=0.40; 95% CI, 0.29-0.56) and in those without any SSA (10.8 vs 4.6; HR=0.35; 95% CI, 0.24-0.50). The PFS benefit with everolimus was observed across all patients subgroups regardless of SSA use (Table). Conclusions: Everolimus significantly prolonged PFS compared with placebo in patients with advanced pNET in this large phase III clinical trial. This benefit was seen across all patient subgroups, including patients receiving prior and on-study SSA treatment.