Results of the PALETTE (PAzopanib ExpLorEd in SofT-Tissue Sarcoma) study presented at the 2011 Annual Meeting of the American Society for Clinical Oncology demonstrated a statistically significant improvement in the time to first occurrence of tumour progression or death (progression free survival or PFS) for study patients treated with the multi-tyrosine kinase inhibitor pazopanib, compared to placebo.

PALETTE is a randomised, double-blind, placebo controlled Phase III trial in patients with metastatic soft tissue sarcomas (excluding gastrointestinal stromal tumours and adipocytic sarcomas) and was jointly conducted by GlaxoSmithKline and the European Organisation for Research and Treatment of Cancer (EORTC) in collaboration with cancer centres across the world.

Use of pazopanib to treat soft tissue sarcomas is investigational and subject to evaluation of benefits and risks by regulatory authorities before being made available for that use.

369 adults with certain metastatic soft tissue sarcomas whose disease had progressed despite treatment with chemotherapy were randomly assigned on a 2 to 1 basis to pazopanib or placebo.

The study showed a 69% reduction in the risk of progression or death in patients who received pazopanib compared to those who received placebo (hazard ratio 0.31 with 95% CI 0.24 to 0.40, p<0.0001).

The median PFS for patients receiving pazopanib was 4.6 months compared 1.5 months for those receiving placebo (p<0.0001).

The PFS benefit for pazopanib seen in the overall population was consistent across three pre-specified subgroups: leiomyosarcoma, synovial sarcoma, and a subgroup of various histologic sarcoma subtypes. Overall survival at the interim analysis was not statistically significant (median 11.9 months pazopanib, 10.4 months placebo; p=0.1782).

"We were motivated to investigate the effects of pazopanib in patients with certain soft tissue sarcomas based on the potential role of angiogenesis in these tumours and the need for new agents that could possibly delay progression of the disease," said Lini Pandite, Vice President and Medicine Development Leader.

In this trial, commonly occurring toxicities (>20%) for pazopanib and placebo respectively were: fatigue (65%;49%), diarrhea (58%;16%), nausea (54%28%), weight loss (48%;20%), hypertension (41%, 7%), loss of appetite (40%;20%). Grade 3-4 toxicities for pazopanib and placebo occurring on therapy were: fatigue (13%;6%), elevations in the liver enzyme ALT (10%;3%), diarrhea (5%;1%), nausea (3%;2%), hypertension (28%;3%), decreased appetite (6%;0). Cardiac dysfunction was reported in 9% of the pazopanib group and 4% of the placebo group.

Venous thromboembolic events were reported in 5% of the pazopanib group and 2% of placebo group. Pneumothorax was reported in 3% of pazopanib patients and 0% of placebo patients. Fatal adverse events occurring on therapy were reported in 5% of the placebo group and 3% of the pazopanib group with one death attributed to pazopanib by the investigator.



Source: GSK