Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043

Abstract

10031 Background: Currently, there is no standard treatment for pts with advanced STS who relapse after or during standard chemotherapy. Since VEGF is involved in the pathogenesis of STS subtypes, pazopanib, a multi-targeted tyrosine kinase inhibitor of VEGF- receptors 1–3, PDGFR-a and β, and c-kit was explored. Methods: Pts had intermediate or high grade advanced or metastatic STS, were ineligible for chemotherapy or had received no more than one combination or 2 single cytotoxic agents for advanced disease. Pts had WHO performance 0–1 and adequate organ function. Progressive disease had to be documented within the last 6 months. Treatment was oral pazopanib at 800 mg daily. Primary end point was progression-free survival at 12 weeks. Secondary end points included response, safety, and overall survival. 4 different strata were studied: leiomyosarcomas, adipocytic STS, synovial sarcomas, and other types of STS. Simon 2-stage design was applied (P1: 40%; P0: 20%; a=β=0.1). Results: As of 11 October, 2006, 111 pts were enrolled. 98.2% had received prior chemotherapy. In 44 pts with validated data no grade 3–4 hematological toxicities were seen, grade 3–4 bilirubin and creatinine elevations in 2 and 1 pts, respectively. Other toxicities (all grades; grade 3–4) were fatigue (53.6%; 9.7%), hypertension (31.7%; 9.7%), and diarrhea (29.3%; 4.8%). Of 80 pts included in the 1 st stages of all 4 strata together, 27 were alive and progression-free at 12 weeks. The 2 nd stage was opened for further accrual in 3 strata. Complete accrual is anticipated in February 2007. Conclusions: In relapsed or refractory advanced STS, pazopanib has acceptable toxicity. These preliminary results justify further investigation of pazopanib in STS. No significant financial relationships to disclose.