Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial
The Lancet, 05/22/2012
van der Graaf WTA et al. – Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy.Methods
- This phase 3 study was done in 72 institutions, across 13 countries.
- Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over.
- Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation.
- The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat.
- 372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123).
- Median progression-free survival was 4·6 months (95% CI 3·7—4·8) for pazopanib compared with 1·6 months (0·9—1·8) for placebo (hazard ratio [HR] 0·31, 95% CI 0·24—0·40; p<0·0001).
- Overall survival was 12·5 months (10·6—14·8) with pazopanib versus 10·7 months (8·7—12·8) with placebo (HR 0·86, 0·67—1·11; p=0·25).
- The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]).
- The median relative dose intensity was 100% for placebo and 96% for pazopanib.