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).

Chawla, Sant P.; Blay, J-Y.; Ray-Coquard, I. L.; Cesne, Axel Le; Staddon, Arthur P.; Milhem, Mohammed; Penel, Nicolas; Riedel, Richard F.; Nguyen, Binh Bui; Cranmer, Lee D.; Reichardt, Peter; Bompas, Emmanuelle; Song, Yan; Lee, R.; Eid, Joseph; Loewy, John W.; Haluska, Frank G.; Dodion, Pierre; Demetri, G. D.

doi:10.1200/jco.2011.29.15_suppl.10005

Cited by 68 publications

(58 citation statements)

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“…Final results of this study confirmed that single-agent ridaforolimus showed clinical benefit in patients with several sarcoma subtypes, with the majority of responders having primary bone sarcomas (17). Results from the recently completed phase 3 Sarcoma mUlti-Center Clinical Evaluation of the Efficacy of riDaforolimus (SUCCEED) trial in patients with advanced sarcoma aged 13 and older showed that maintenance therapy with ridaforolimus (40 mg orally, once daily for 5 consecutive days every week) significantly improved progression-free survival (PFS) compared with placebo and had a safety profile consistent with other mTOR inhibitors (16).…”

Section: Introductionmentioning

confidence: 99%

“…In preclinical studies, ridaforolimus displayed antiproliferative activity against a variety of human tumor cells lines in vitro and tumor xenograft models in vivo, with additive or synergistic activity when combined with other anticancer agents (14,15). In phases 2 and 3 clinical trials, ridaforolimus has shown promising activity in adults with advanced sarcomas and other malignancies (16)(17)(18)(19)(20)(21). In a large phase 2 study evaluating 212 patients with advanced sarcomas, clinical benefit with intravenously (i.v.)…”

Section: Introductionmentioning

confidence: 99%

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A Multicenter, First-in-Pediatrics, Phase 1, Pharmacokinetic and Pharmacodynamic Study of Ridaforolimus in Patients with Refractory Solid Tumors

Gore

Trippett

Katzenstein

et al. 2013

Clinical Cancer Research

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Purpose: Ridaforolimus (MK-8669, AP23573) is a potent and selective mammalian target of rapamycin (mTOR) inhibitor. Preclinically, ridaforolimus displays antiproliferative activity against a variety of human tumors in vitro and tumor xenograft models in vivo, with additive or synergistic activity when combined with other anticancer agents. Antitumor activity has been confirmed in adults. This phase I study determined the safety, pharmacological, biologic, and toxicity profiles of ridaforolimus in pediatric patients with refractory malignancies.Experimental Design: Eligible children ages 1 to 18 years with advanced solid tumors were enrolled in a 3 þ 3 dose escalation design, to determine the safety, tolerability, and maximum tolerated dose (MTD)/ dose-limiting toxicity (DLT) of ridaforolimus. Toxicities, pharmacokinetics, and pharmacodynamics were characterized.Results: Fifteen patients were treated. No DLT was observed at any dose level tested; therefore, an MTD was not identified. Most adverse events were mild to moderate; the most common grades 3 and 4 adverse events were hematologic, including thrombocytopenia and anemia. Nonhematologic adverse events were mostly electrolyte disturbances. The observed pharmacokinetic profile of ridaforolimus in children was consistent with that previously showed in adults. Pharmacodynamic confirms that the dose range tested has pharmacological/pharmacodynamic activity. Forty percent of patients achieved stable disease including four of six with central nervous system tumors and two of eight with sarcomas.Conclusions: This first-in-pediatrics study shows that the second-generation mTOR inhibitor ridaforolimus is well tolerated in heavily pretreated children with refractory solid tumors. No DLTs were observed over the dose range tested. Ridaforolimus may represent a therapeutic option for use in pediatric malignancies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Multicenter, First-in-Pediatrics, Phase 1, Pharmacokinetic and Pharmacodynamic Study of Ridaforolimus in Patients with Refractory Solid Tumors

Gore

Trippett

Katzenstein

et al. 2013

Clinical Cancer Research

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“…Ridaforolimus, a rapamycin analog, has been studied in sarcomas and may confer stability of disease while not having the adverse toxicities of combination chemotherapy (68)(69)(70)(71). The SUCCEED trial has studied this drug at multiple centers (72).…”

Section: Chemotherapy and Targeted Therapymentioning

confidence: 99%

Multimodality therapy for metastatic sarcomas confined to the lung

Gollard

Turner

2012

Oncology Letters

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Abstract. Metastectomy or resection of sarcomas which have metastasized to the lung from other sites has a long and established history. At present, there are more than forty different drugs with activity in soft tissue sarcomas. A number of sarcomas demonstrate differential sensitivities to chemotherapy and targeted agents. Intimate knowledge of the biological behavior of each distinct type of sarcoma should predicate what treatment or protocol is most suitable. Certain patients might benefit from either neoadjuvant or adjuvant therapy following the resection of metastatic lesions. Much remains to be learned about the differential sensitivities of various sarcomas to different treatment regimens.

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“…Subgroup analysis including histology, number of prior lines of therapy, etc is pending. 66 A combined phase I/II study combining everolimus and imatinib in pretreated metastatic GIST patients was reported. The recommended phase II dose of the combination was 2.5 mg daily of everolimus in combination with 600 mg daily of imatinib, denoting pharmacokinetic interaction.…”

Section: Pi3k/akt/mtor Pathwaymentioning

confidence: 99%