Abstract
Phase III, placebo-controlled trial (SUCCEED) evaluating ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy: Long-term (≥ 24 months) overall survival results
Journal of clinical oncology, Vol.30(15_suppl), pp.10010-10010
05/20/2012
DOI: 10.1200/jco.2012.30.15_suppl.10010
Abstract
10010
Background: The mammalian target of rapamycin (mTOR) regulates cell growth and proliferation and is abnormally activated in many sarcomas. Ridaforolimus, an oral mTOR inhibitor, demonstrated clinical activity in previous nonrandomized trials in advanced sarcomas following failure of prior chemotherapy. Methods: An international, multicenter, placebo-controlled, phase 3 trial was conducted to evaluate maintenance therapy with ridaforolimus in patients with metastatic soft-tissue or bone sarcomas who achieved disease control from prior chemotherapy. Patients were randomized (1:1) to receive oral ridaforolimus (40 mg) or placebo once daily for 5 days each week. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety and tolerability. For OS, patients were to be followed at 3-month intervals for at least 24 months and up to 60 months after randomization. Results: 702 of 711 randomized patients received treatment. At the time of the data cutoff for OS (386 deaths), patients in the study population had been followed for at least 15 months. Median OS was 93.3 weeks with ridaforolimus vs 83.4 weeks with placebo (hazard ratio [HR]=0.88; 95% confidence interval [CI]: 0.72, 1.08; P=0.23). Ridaforolimus significantly improved PFS vs placebo (HR=0.72; 95% CI: 0.61, 0.85; P=0.0001; median PFS: 17.7 weeks vs 14.6 weeks); PFS improved across all prespecified baseline characteristics. As expected from the class of mTOR inhibitors, the most common adverse events with ridaforolimus were stomatitis, thrombocytopenia, noninfectious pneumonitis, hypertriglyceridemia, hyperglycemia, infections, and rash. Conclusions: Oral ridaforolimus was generally well-tolerated and significantly improved PFS in metastatic sarcoma patients with benefit from prior chemotherapy, offering an effective treatment alternative to surveillance alone. Results of a long-term OS analysis (prespecified to occur at 67% mortality, 24 months minimum follow-up) in the intent-to-treat population will be available in early 2012.
Details
- Title: Subtitle
- Phase III, placebo-controlled trial (SUCCEED) evaluating ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy: Long-term (≥ 24 months) overall survival results
- Creators
- Jean-Yves Blay - Centre Léon BérardSant P. Chawla - Sarcoma Oncology CenterIsabelle Ray-Coquard - Centre Léon BérardAxel Le Cesne - Institut Gustave RoussyArthur P. Staddon - University of PennsylvaniaMohammed M. Milhem - University of IowaNicolas Penel - Centre Oscar LambretRichard F. Riedel - Duke Medical CenterBinh Bui Nguyen - Institut BergoniéLee D. Cranmer - University of ArizonaPeter Reichardt - Helios Hospital Bad SaarowEmmanuelle Bompas - Centre René Gauducheau, Nantes, FranceThierry Alcindor - McGill University Health CentreDaniel A. Rushing - Indiana University – Purdue University IndianapolisYang Song - MSDScot Ebbinghaus - MSDFrank G. Haluska - ARIAD Pharmaceuticals, Inc.Pierre F. Dodion - ARIAD Pharmaceuticals, Inc.George D. Demetri - Dana-Farber Cancer Institute
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.30(15_suppl), pp.10010-10010
- DOI
- 10.1200/jco.2012.30.15_suppl.10010
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363167002771
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