IMATINIB IN OTHER SARCOMAS THAN GIST

J Clin Oncol. 2009 May 18. [Epub ahead of print]

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Phase II Multicenter Trial of Imatinib in 10 Histologic Subtypes of Sarcoma Using a Bayesian Hierarchical Statistical Model.

Chugh R, Wathen JK, Maki RG, Benjamin RS, Patel SR, Myers PA, Priebat DA, Reinke DK, Thomas DG, Keohan ML, Samuels BL, Baker LH.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI; The University of Texas M. D. Anderson Cancer Center, Houston, TX; Memorial Sloan-Kettering Cancer Center; New York, NY; Washington Cancer Institute, Washington, DC; and Kootenai Cancer Center, Coeur d'Alene, ID.

PURPOSE: The purpose of this trial was to assess the efficacy of imatinib in patients with one of 10 different subtypes of advanced sarcoma. PATIENTS AND METHODS: Eligible patients were treated daily with imatinib dosed at 300 mg twice a day (for body-surface area >/= 1.5 m(2)). The primary end point was response (clinical benefit response [CBR]), defined as complete (CR) or partial response (PR) at 2 months, or stable disease, CR, or PR at 4 months. Rules for early termination within each disease type were based on a Bayesian hierarchical probability model (BHM) accounting for correlation of the responses of the 10 subtypes. Available tissue samples were analyzed for molecules within the KIT/platelet-derived growth factor receptor (PDGFR) signal transduction pathway. RESULTS: One hundred eighty-five assessable patients with one of 10 subtypes of sarcoma were treated. One CR and three PRs were achieved. A CBR was achieved in 28 patients treated overall and by subtype: two angiosarcomas (n = 16), 0 Ewing (n = 13), one fibrosarcoma (n = 12), six leiomyosarcomas (n = 29), seven liposarcomas (n = 31), three malignant fibrous histiocytomas (n = 30), five osteosarcomas (n = 27), one malignant peripheral-nerve sheath tumor (n = 7), 0 rhabdomyosarcoma (n = 2), and three synovial sarcomas (n = 22). Variable expression and mutations within the KIT/PDGFR pathway were observed. CONCLUSION: This is the first phase II study of a new agent in sarcoma to include sufficient patients with each of the common histologic subtypes to permit generalizable conclusions. The BHM is an effective method for studying rare diseases and their subtypes, when it is reasonable to assume that their response rates are exchangeable. Although rare dramatic responses were seen, imatinib is not an active agent in advanced sarcoma in these subtypes.