Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT).

Published

Journal Article

10005 Background: The mTOR signaling pathway is activated in most sarcomas. R, an oral mTOR inhibitor, demonstrated activity in phase I-II trials in advanced sarcomas following failure of prior CT. 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 metastatic sarcoma (stratified soft-tissue vs bone; 1st vs, 2nd/3rd line prior CT) following stable disease or better response to prior CT. Primary endpoint is progression-free survival (PFS) based on independent radiological review (IRR). Secondary endpoints include overall survival (OS), best target lesion response, cancer-related symptoms, and safety and tolerability. RESULTS: 711 pts were randomized from Jun '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 OS is ongoing; results at data cut-off (313 OS events) indicate a trend favoring R (median OS: 88.0 wks R vs. 78.7 wks P; HR=0.92, 95% CI (0.74, 1.15)). While incidence of stomatitis (52%) and other adverse events was higher in pts receiving R, the overall safety profile was consistent with other mTOR inhibitors. CONCLUSIONS: This randomized trial of ridaforolimus met the primary endpoint of improved PFS in pts with metastatic soft-tissue or bone sarcomas to maintain benefit from prior standard CT. The rapid progression of metastatic sarcomas demonstrates the aggressive nature of these malignancies, and maintenance therapy with R will provide a new option for pts with this life-threatening disease.

Full Text

Duke Authors

Cited Authors

  • Chawla, SP; Blay, J; Ray-Coquard, IL; Le Cesne, A; Staddon, AP; Milhem, MM; Penel, N; Riedel, RF; Bui Nguyen, B; Cranmer, LD; Reichardt, P; Bompas, E; Song, Y; Lee, R; Eid, JE; Loewy, J; Haluska, FG; Dodion, PF; Demetri, GD

Published Date

  • May 20, 2011

Published In

Volume / Issue

  • 29 / 15_suppl

Start / End Page

  • 10005 -

PubMed ID

  • 28021073

Pubmed Central ID

  • 28021073

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Language

  • eng

Conference Location

  • United States