Background: Advanced neuroendocrine tumors (NET) arise from diverse sites of origin, including GI tract, lung, and pancreas. Nearly 50% of new NET cases are advanced, and 5-year survival rates vary, depending on the primary site of disease. In the RADIANT-2 trial, everolimus, an oral mTOR inhibitor, plus octreotide LAR (E+O) provided a clinically meaningful 5.1-month increase in median progression-free survival (PFS) compared with placebo + octreotide LAR (P+O) in patients with advanced NET (ESMO 2010 Abstract LBA8). Here we present an exploratory analysis of PFS by primary tumor site in the RADIANT-2 patient population. Methods: Patients (n=429) with well or moderately differentiated advanced NET and a history of secretory symptoms associated with carcinoid syndrome received oral everolimus 10 mg/d + octreotide LAR 30 mg intramuscularly q28d (n=216) or P+O (n=213). The primary endpoint was PFS per central review (RECIST v1.0). The primary tumor site was identified in each treatment arm. Analysis was performed to determine the association between primary tumor site and PFS. Results: Small intestine, lung, and colorectal were the primary tumor sites in 224 (111 E+O; 113 P+O), 44 (33 E+O; 11 P+O), and 39 (19 E+O; 20 P+O) patients. Median PFS was longer in the E+O arm than in the P+O arm in all three groups (Table). E+O improved median PFS compared with P+O by 4.6 months in small intestine, 8.0 months in lung, and 23.3 in colorectal subgroups. Conclusions: Everolimus plus octreotide LAR demonstrates a clinically meaningful prolongation of median PFS in patients with well or moderately differentiated advanced NET, including patients with primary tumor sites associated with a poorer prognosis, such as lung and colorectal cancer.