Panneerselvam, Ashok

224 Background: In the phase 3 RADIANT-3 trial, everolimus (EVE) demonstrated significantly improved median progression-free survival (PFS) versus placebo (PBO) (11.0 vs 4.6 months; HR=0.35, p < 0.0001) in patients (pts) with pancreatic neuroendocrine tumors (pNET) (Yao et al, NEJM, 2011). Here we present a planned exploratory analysis by prior chemotherapy (chemo) use. Methods: Pts with progressive low- or intermediate-grade pNET were prospectively stratified by prior chemo use and randomized (1:1) to EVE 10 mg/d (n = 207) or PBO (n = 203) plus best supportive care. Results: Of the 410 pts, 206 (50%) had received prior chemo and 204 (50%) were chemo naive. Baseline characteristics (age, sex, race, tumor type, histologic grade) and baseline tumor biomarker levels were similar for pts with/without prior chemo. More chemo-naive pts were newly diagnosed (time since initial diagnosis ≤ 6 mo: 50 [25%] vs. 7 [3%] pts with prior chemo). A lower proportion of chemo-naive pts received prior somatostatin therapy (45% vs. 54% prior chemo). EVE significantly prolonged median PFS regardless of prior chemo use (with prior chemo: 11.0 vs. 3.2 months; HR = 0.35, 95% CI 0.25-0.49, p < 0.001; chemo naive: 11.4 vs. 5.4 months; HR = 0.42, 95% CI 0.29-0.60; p < 0.001). Stable disease was the best overall response in 73% of EVE-treated pts irrespective of prior chemo use. The benefit from EVE irrespective of prior chemo was further demonstrated by disease stabilization or minor tumor shrinkage and in the lower incidence of progressive disease in waterfall plots. Safety of EVE was consistent regardless of prior chemo use. The most common drug-related adverse events (chemo vs chemo naive) included rash (53% vs. 52%), stomatitis (52% vs. 56%), diarrhea (41% vs. 52%), and fatigue (37% vs. 51%). Conclusions: This planned subgroup analysis demonstrated the beneficial effects of EVE in pts with pNET regardless of prior chemo use. These findings support the possible first-line use of EVE for pts with pNET.

AbstractIntroduction.The incidence of colorectal neuroendocrine tumors (NETs) is increasing, and patients 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 the everolimus plus octreotide LAR arm than in the placebo plus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotide LAR was generally 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.