PHASE III TRIAL OF EVEROLIMUS IN ADVANCED PANCREATIC NEUROENDOCRINE TUMORS (RADIANT-3): OVERALL POPULATION AND JAPANESE SUBGROUP ANALYSIS

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Abstract

Background

In the phase III RADIANT-3 trial, everolimus (RAD001), an oral mTOR inhibitor, demonstrated a statistically and clinically significant improvement in progression-free survival (PFS) over placebo in patients with advanced pancreatic neuroendocrine tumors (pNET). The purpose of this presentation is to show the efficacy and safety in the Japanese subgroup analysis.

Methods

The subgroup analysis for the Japanese patients (n = 40) was carried out comparing everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17); both in conjunction with best supportive care (BSC), in the following end points: PFS, disease control rate (DCR), adverse drug reaction (ADR) and median duration of exposure.

Results

PFS was significantly prolonged in patients treated with everolimus compared with placebo (hazard ratio, 0.19; 95% confidence interval (CI), 0.08–0.48; log-rank P < 0.001) with a median of 19.45 months (95% CI, 8.31–not available) in the everolimus arm and 2.83 months (95% CI, 2.46–8.34) in the placebo arm. DCR was 86.9% in the everolimus arm and 35.3% in the placebo arm. The majority of ADRs were grade 1 or 2 in severity. Most common ADRs in the everolimus arm were rash (n = 20; 87%), stomatitis (n = 17; 74%) and infections (n = 15, 65%). Grade 3/4 ADRs occurred in 69.5% of the everolimus arm and 29.4% of the placebo arm. The most frequent grade 3/4 ADRs were neutropenia (% in the everolimus arm; 17.4% versus % in the placebo arm; 17.6%), anemia (8.7% versus 0%), pneumonitis (8.7% versus 0%) and leukopenia (8.7% versus 0%). The median duration of exposure to everolimus was 60 versus 12 weeks on placebo. Treatment discontinuation for ADR was 17% in the everolimus arm versus 0% in the placebo arm.

Conclusions

Everolimus demonstrated a statistically and clinically meaningful improvement in PFS over placebo and was well tolerated in Japanese patients. These results suggest that everolimus can be a standard treatment of Japanese patients with advanced pNET.

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