A randomized, double-blind, placebo-controlled phase III trial of @entity4381 in the prevention of XXXX in Japanese @entity1 with bone metastases from @entity0 .

@entity5921 @entity1 @entity0 @entity174 @entity2741 @entity5 @entity1295 @entity532 @entity1745 @entity1011 @entity4841 @entity4381 @entity221 @entity1141
UNASSIGNED: 668 Background: In Western populations, @entity4381 ( @entity5921 ) has been proven effective for the prevention of @entity1141 ( @entity1141 ) from bone metastases. For @entity0 @entity1 , @entity5921 was shown to be superior to pamidronate. However, the efficacy of @entity5921 is unknown in Japanese @entity1 . We report here data from the first randomized, placebo-controlled study of @entity5921 in Japanese @entity1 . METHODS: Japanese @entity1 with bone metastases from @entity0 were randomized to either @entity5921 4mg i.v. infusion over 15 min every 4 weeks or placebo (P). The primary efficacy endpoint was SRE rate ratio (ratio of number of @entity1141 per year for @entity5921 -treated @entity1 over that for placebo) at 1 year. @entity1141 included pathologic @entity174 , @entity1745 , and surgery to treat or prevent @entity174 . Secondary endpoints included proportion of @entity1 with >= 1 SRE, time to first SRE and multiple event analysis (MEA: A-G model). @entity5 induced @entity2741 was included in the SRE composite in secondary endpoints. Safety was assessed according to NCI-CTC. RESULTS: 227 @entity1 (median age 53 years) were accrued to the study with 114 in the @entity5921 arm and 113 in the P arm. @entity1 were well matched with regard to baseline clinical characteristics. The primary endpoint, SRE rate ratio was 0.61 (p=0.027), indicating that SRE rate was reduced by 39% with @entity5921 . Proportions of @entity1 with >= 1 SRE were 30.7% and 52.2% for the @entity5921 and P group, respectively (p=0.001). Median time to first SRE were 360 days in the P group while it did not reach in the @entity5921 group (p=0.004). Risk ratio of @entity5921 to P was 0.56 by MEA (p=0.009). @entity5921 was well tolerated. The most common adverse effects observed more frequently in the @entity5921 vs. P group were @entity221 (55% vs. 33%), @entity1295 (44.5% vs. 31.9%) and @entity4841 (21.1% vs. 15.9%). One @entity1 in the @entity5921 group (0.9%) experienced increased serum @entity1011 . CONCLUSIONS: @entity5921 4mg demonstrated significant clinical efficacy in Japanese @entity1 for preventing @entity532 with bone metastases, with an overall 44% reduction in the risk of experiencing @entity1141 as shown by MEA. [Table: see text].
