Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: A subgroup analysis of the phase III RADIANT-2 study

Introduction. The incidence of colorectal neuroendocrine tumors(NETs) is increasing,andpatients with this disease have particularly poor prognoses. Treatment options are limited, and survival times have not improved in the past decade. Methods. A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long-acting repeatable (LAR) was conducted in patients with colorectal NETs enrolled in the phase III RAD001 in Advanced Neuroendocrine Tumors, Second Trial (RADIANT-2) study. The primary endpoint (progression- free survival [PFS]), secondary endpoints (including objective response rate), and safety were assessed. Results. Patients with colorectal NETs receiving everolimus plus octreotide LAR had a significantly longer median PFS (29.9 months; n=19) than did those receiving placebo plus octreotide LAR (6.6 months; n = 20). Everolimus plus octreotide LAR treatment also significantly reduced the risk for disease progression (hazard ratio: 0.34; 95% confidence interval: 0.13- 0.89; p=.011). Although no objective responses were observed, tumor shrinkage was more frequently noted in theeverolimusplusoctreotideLARarmthanintheplaceboplus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotideLARwasgenerally well tolerated by patients with colorectal NETs; rash and stomatitis were the most commonly reported adverse events. Conclusions. Everolimus plus octreotide LAR treatment had significant benefits and improved outcomes for patients with advanced colorectal NETs compared with placebo plus octreotide LAR treatment. Results of this exploratory analysis are consistent with those reported from the RADIANT-2 primary analysis. These findings support additional investigations of everolimus plus octreotide LAR in patients with colorectal NETs.