Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65 risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n 23) and matching placebo (n 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95 confidence interval, 8.31not available) with everolimus vs 2.83 months (95 confidence interval, 2.468.34) with placebo, resulting in an 81 risk reduction in progression (hazard ratio, 0.19; 95 confidence interval, 0.080.48; P 0.001). Adverse drug reactions occurred in all 23 (100) Japanese patients receiving everolimus and in 13 (77) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n 20; 87), stomatitis (n 17; 74), infections (n 15; 65), nail disorders (n 12; 52), epistaxis (n 10; 44) and pneumonitis (n 10; 44). These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours.