Originally published as JCO Early Release 10.1200/JCO.2008.21.3223 on May 18 2009

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Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)

From the Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Medical Oncology, Centre Leon Berard, Lyon; Department of Medical Oncology, Institute Gustave Roussy, Villejuif; and Department of Pathology, Center Georges-François-Leclerc, Dijon, France; Department of Medical Oncology, National Medical Center, Budapest, Hungary; Department of Medical Oncology, Royal Marsden Hospital, London, United Kingdom; Department of General Medical Oncology, Catholic University of Leuven, Leuven; and European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium; and GlaxoSmithKline, Research Triangle Park, NC.

Corresponding author: Stefan Sleijfer, MD, PhD, Dept of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands; e-mail: s.sleijfer{at}erasmusmc.nl.

Purpose Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS.

Patients and Methods Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR_{12 weeks}). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; = β = .1) for each stratum.

Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR_{12 weeks}, five [26%] of19). PFR_{12 weeks} was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%).

Conclusion Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; the 13th Annual Meeting of the Connective Tissue Oncology Society, November 1-3, 2007, Seattle, WA; and the 33rd European Society of Medical Oncology Congress, September 12-16, 2008, Stockholm, Sweden.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available JCO.org.

Clinical trial information can be found for the following: NCT00297258 [ClinicalTrials.gov] .

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