1132OEVEROLIMUS (EVE) FOR THE TREATMENT OF ADVANCED PANCREATIC NEUROENDOCRINE TUMORS (PNET): FINAL OVERALL SURVIVAL (OS) RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO (PBO)-CONTROLLED, MULTICENTER PHASE III TRIAL (RADIANT-3)

ABSTRACT Aim: EVE significantly improved median progression-free survival vs PBO in patients (pts) with pNET by 6.4 months in RADIANT-3 (11.0 vs 4.6 months; HR 0.35, 95% CI 0.27-0.45; p Methods: Pts with progressive advanced, low- or intermediate-grade pNET were randomized to EVE 10mg/d (n = 207) or PBO (n = 203); both with best supportive care. Upon disease progression during double-blind phase, crossover from PBO to open-label EVE was allowed. At the time of unblinding (cutoff, Jun 3, 2010), all ongoing pts transitioned into the extension phase to receive open-label EVE. After 256 events, OS analysis was performed using a stratified log-rank test in the intent-to-treat patient population (N = 410; all randomized pts). Results: Of 410 pts, 225 switched to open-label EVE; including 85% of pts initially randomized to PBO (172 of 203). Median open-label EVE exposure was 67.1 weeks (range 1-189) in pts initially randomized to EVE and 44.0 weeks (range 0-261) in pts randomized to PBO. Median OS (95% CI) was 44.0 (35.6-51.8) months for EVE arm and 37.7 (29.1-45.8) months for PBO arm (HR 0.94, 95% CI 0.73-1.20; p = 0.30; boundary 0.0249). Adverse events reported during the open-label phase (n = 221) were consistent with those observed during blinded treatment; the most common included stomatitis (47%), diarrhea (44%), and rash (40%). Estimated OS rates Kaplan-Meier estimates [95% CI] at: EVE 10 mg/d (n = 207) PBO (n = 203) 12 mo 82.6 [76.6-87.2] 82.0 [75.9-86.7] 24 mo 67.7 [60.7-73.8] 64.0 [56.8-70.2] 36 mo 56.7 [49.4-63.3] 50.9 [43.6-57.7] 48 mo 46.9 [39.7-53.8] 41.3 [34.3-48.1] 60 mo 34.7 [27.7-41.7] 35.5 [28.7-42.4] Conclusions: EVE demonstrated a median OS of 44 months, the longest OS reported for progressive advanced pNET pts in a phase 3 study. A clinically important improvement of 6.3 months in median OS vs PBO was observed, although the difference did not reach statistical significance. Crossover of majority of pts (85%) may also have confounded OS. The safety of EVE was consistent with previous experience. Disclosure: J.C. Yao: Corporate-sponsored research (Novartis); Consultancy (Novartis); M. Pavel: Honoraria for advisory board meeting and presentations (Novartis, IPSEN, Pfizer); Research grant (Novartis); C. Lombard-Bohas: Membership on an advisory board or board of directors (Novartis); E. van Cutsem: Research grant paid to university by Novartis; D. Lam: Employee (Novartis); Stock ownership (Novartis); T. Kunz: Employee (Novartis); Stock ownership (Novartis); U. Brandt: Employee (Novartis); Stock ownership (Novartis); E.G.E. De Vries: Support for the execution of the trial made available to the UMCG; T. Hobday: Research funding (Novartis); R. Pommier: Consultant (Novartis, Pfizer). All other authors have declared no conflicts of interest.