Pazopanib: in advanced soft tissue sarcoma

Pazopanib inhibits multiple receptor tyrosine kinases, through which it mediates antiangiogenic and antitumour effects. 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 (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) ≈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 tumour was low/intermediate or high grade and regardless of tumour histology (leiomyosarcoma, synovial sarcoma, other STS), although patients with adipocytic STS were among those 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 final analysis of the PALETTE trial, median overall survival was ≈2 months longer with pazopanib than with placebo, although this between-group difference was not statistically significant. Oral pazopanib generally had no detrimental effect on health-related quality of life and had an acceptable tolerability profile in patients with STS in the PALETTE trial, with adverse events generally being grade 1 or 2 in severity.