Pazopanib as new therapeutic option in therapy of advanced soft tissue sarcoma

Abstract

Pazopanib inhibits multiple receptor tyrosine kinases, through which it mediates antiangiogenic and antitumor effects. Approved by the Food and Drug Administration in 2009 in the United States for the treatment of metastatic renal cell carcinoma, pazopanib has been tested in advanced or metastatic soft-tissue sarcoma. The clinical efficacy of oral pazopanib in patients with metastatic soft tissue sarcoma (STS) was demonstrated in a randomized, double-blind, placebo-controlled, phase III trial (EORTC 62072, VEG110727, PALETTE), generally confirming the findings of an earlier, noncomparative phase II study. In the multicentre PALETTE trial, pazopanib 800 mg once daily significantly prolonged median progression-free survival (PFS; primary endpoint) approximately 3-fold relative to placebo (4.6 vs 1.6 months) in adults with progressive metastatic STS following standard chemotherapy. According to subgroup analyses, pazopanib provided benefit over placebo in terms of PFS regardless of whether the tumor was low/intermediate or high grade and regardless of tumor histology (leiomyosarcoma, synovial sarcoma, otherSTS), although patients with adipocytic STS were excluded from the PALETTE trial, as sufficient benefit had not been shown with the drug in patients with adipocytic STS in the phase II study. At the final analysis of the PALETTE trial, median overall survival was about 2 months longer with pazopanib than with placebo, although this difference was not statistically significant. Oral pazopanib generally had no detrimental effect on health-related quality of lifeand had an acceptable tolerability profile in patients with STS in the PALETTE trial, with adverse events generally being grade 1 or 2 in severity. Currently pazopanib is approved by FDA and EMA for the treatment of metastatic STS in patients which received chemotherapy, exceptional gastrointestinal stromal tumor and liposarcoma. This review focuses on the development of this new agent in the treatment of metastatic STS as well as it describes authors’ experience in therapy of advanced STS with pazopanib.