UNASSIGNED: 10005 Background: The @entity3470 signaling pathway is activated in most @entity242 . R, an oral @entity3470 inhibitor, demonstrated activity in phase I-II trials in advanced @entity242 following failure of prior @entity7730 . METHODS: This trial is an international, double-blind study randomized 1:1 between R (40 mg orally for 5 days/week) vs. placebo (P) as maintenance therapy in pts with @entity3 (stratified soft-tissue vs bone; 1st vs, 2nd/3rd line prior @entity7730 ) following stable disease or better response to prior @entity7730 . Primary endpoint is progression-free survival (PFS) based on independent radiological review (IRR). Secondary endpoints include @entity1349 ( @entity1349 ), @entity3987 response, @entity5 , and safety and tolerability. RESULTS: 711 pts were randomized from @entity1178 '07 to Jan '10 and analyzed for efficacy. At data cut-off, 53 pts remained on blinded drug. Baseline characteristics were well balanced between the study arms. Analysis of 552 PFS events per IRR showed that R met the prespecified study endpoint with a statistically significant improvement in PFS compared to P (Hazard Ratio HR=0.72, P=0.0001, stratified log-rank). Median PFS improved by 21% (17.7 wks R vs. 14.6 wks P). Based on local site assessment of PFS, R demonstrated an improvement with HR=0.69 (P<0.0001) and a 52% gain in median (22.4 wks R vs. 14.7 wks P). PFS benefit was noted across all prespecified strata. Follow-up for @entity1349 is ongoing; results at data cut-off (313 @entity1349 events) indicate a trend favoring R (median @entity1349 : 88.0 wks R vs. 78.7 wks P; HR=0.92, 95% CI (0.74, 1.15)). While incidence of @entity3136 (52%) and other adverse events was higher in pts receiving R, the overall safety profile was consistent with other @entity3470 inhibitors. CONCLUSIONS: This randomized trial of @entity39426 met the primary endpoint of improved PFS in pts with metastatic soft-tissue or @entity79 to maintain benefit from prior standard @entity7730 . The rapid progression of @entity3 demonstrates the aggressive nature of these @entity5 , and maintenance therapy with R will provide a new option for pts with this life-threatening disease.

Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the @entity3470 inhibitor XXXX (R) as maintenance therapy in advanced @entity242 patients (pts) following clinical benefit from prior standard cytotoxic @entity7730 ( @entity7730 ).

@entity3136 :: ('MESH:D013280', 'Disease') :: ['stomatitis'] @entity242 :: ('MESH:D012509', 'Disease') :: ['sarcomas'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer-related symptoms', 'malignancies'] @entity39426 :: ('MESH:C515074', 'Chemical') :: ['ridaforolimus'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone sarcomas'] @entity1178 :: ('3725', 'Gene') :: ['Jun'] @entity3987 :: ('MESH:D057826', 'Disease') :: ['best target lesion'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic sarcomas', 'metastatic sarcoma'] @entity7730 :: ('MESH:D064146', 'Disease') :: ['CT'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival']
@entity39426 :: (MESH:C515074,Chemical) :: ['ridaforolimus']
