Everolimus for advanced pancreatic neuroendocrine tumours: a subgroup analysis
evaluating Japanese patients in the RADIANT-3 trial.
Author(s): Ito T, Okusaka T, Ikeda M, Igarashi H, Morizane C, Nakachi K, Tajima T, Kasuga A,
Fujita Y, Furuse J.
Affiliation(s): Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi,
Higashi-ku, Fukuoka, Japan. itopapa@intmed3.med.kyushu-u.ac.jp
Publication date & source: 2012, Jpn J Clin Oncol. , 42(10):903-11
OBJECTIVE: 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.
METHODS: 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.
RESULTS: Progression-free survival was significantly prolonged with everolimus
compared with placebo. The median progression-free survival was 19.45 months (95%
confidence interval, 8.31-not available) with everolimus vs 2.83 months (95%
confidence interval, 2.46-8.34) with placebo, resulting in an 81% risk reduction
in progression (hazard ratio, 0.19; 95% confidence interval, 0.08-0.48; 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%).
CONCLUSIONS: These results support the use of everolimus as a valuable treatment
option for Japanese patients with advanced pancreatic neuroendocrine tumours.
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