Pazopanib is a new treatment option for persons with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy, indicate the results of a recent study that saw the drug increase progression-free survival (PFS) almost threefold compared with placebo. However, no significant gains were made in overall survival.
Soft-tissue sarcomas are relatively rare and account for just 1% of all adult cancers, with approximately 11,000 new cases in the United States each year, according to a statement issued by The Lancet Oncology to announce the study findings (2012;379:1879-1886). In advanced stages of the disease, median overall survival is about 12 months. Little progress in developing new treatments has been made over the past 30 years, but recently, pazopanib, a multitargeted tyrosine kinase inhibitor and the first active oral agent for patients with soft-tissue sarcomas other than liposarcomas and gastrointestinal stromal tumors (GISTs), has shown promising activity.
Winette TA van der Graaf, MD, of Radboud University Nijmegen Medical Centre, Netherlands, and colleagues conducted the phase 3 PALETTE study of pazopanib in 72 institutions across 13 countries. The research, which was funded by Votrient (pazopanib) maker GlaxoSmithKline, involved 369 patients with angiogenesis-inhibitor-naïve metastatic soft-tissue sarcoma that was progressing despite previous standard chemotherapy. The participants were randomized in a 2:1 ratio to receive either pazopanib 800 mg once daily (246 patients) or placebo (123 patients).
At a median follow-up of 15 months, median progression-free survival was 4.6 months for pazopanib compared with 1.6 months for placebo. However, overall survival did not increase significantly (12.5 months for pazopanib vs 10.7 months for placebo).
The most common adverse events were:
- fatigue, occurring in 155 (65%) of the pazopanib users vs 60 (49%) of the placebo users
- diarrhea, in 138 (58%) pazopanib users vs 20 (16%) placebo users
- nausea, in 129 (54%) pazopanib users vs 34 (28%) placebo users
- weight loss, in 115 (48%) pazopanib users vs 25 (20%) placebo users
- hypertension, in 99 (41%) pazopanib users vs 8 (7%) placebo users.