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.

Session Type and Session Title: 
Poster Discussion Session, Sarcoma
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 10010)
Jean-Yves Blay, Sant P. Chawla, Isabelle Ray-Coquard, Axel Le Cesne, Arthur P. Staddon, Mohammed M. Milhem, Nicolas Penel, Richard F. Riedel, Binh Bui Nguyen, Lee D. Cranmer, Peter Reichardt, Emmanuelle Bompas, Thierry Alcindor, Daniel A. Rushing, Yang Song, Scot Ebbinghaus, Frank G. Haluska, Pierre F. Dodion, George D. Demetri; University Claude Bernard Lyon I, Centre Léon Bérard, Lyon, France; Sarcoma Oncology Center, Santa Monica, CA; Centre Léon Bérard, Lyon, France; Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; University of Pennsylvania, Philadelphia, PA; University of Iowa Hospital and Clinics, Iowa City, IA; Centre Oscar Lambret, Lille, France; Duke Cancer Institute, Duke University Medical Center, Durham, NC; Institut Bergonie, Bordeaux, France; University of Arizona Cancer Center, Tucson, AZ; HELIOS Klinikum Bad Saarow, Bad Saarow, Germany; Centre René Gauducheau, Nantes, France; McGill University Health Centre, Montreal, QC, Canada; Indiana University, Indianapolis, IN; Merck & Co., Inc., Whitehouse Station, NJ; Merck Research Laboratories, North Wales, PA; ARIAD Pharmaceuticals, Cambridge, MA; Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA

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Abstract Disclosures


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.