GlaxoSmithKline announced the results of a phase-III study demonstrating that pazopanib reduced the risk of tumour progression or death by 54 per cent compared to placebo.
Study findings demonstrated that the median time without tumour growth or death (progression free survival or PFS) in the pazopanib treated group was 9.2 months compared to 4.2 months in the placebo group. When specific patient groups were evaluated, those with no prior drug treatment experienced 11.1 months of median PFS with pazopanib versus 2.8 months with placebo. Patients who had previously received cytokine-based treatment showed 7.4 months of median PFS with pazopanib versus 4.2 months with placebo. These results were featured in an oral presentation at the annual American Society for Clinical Oncology (ASCO) meeting in Orlando, Florida.
"The study shows that pazopanib significantly improved PFS for patients regardless of whether or not they had prior therapy. While there have been many treatment advances for patients with advanced kidney cancer, there is still a need for medicines that are effective and well-tolerated," said Dr Cora N Sternberg, Department of Medical Oncology, San Camillo and ForlaniniHospitals, Rome, Italy. "Additionally, patients did not experience a significant decline in health-related quality of life with no significant differences between pazopanib and placebo."
The results are based on a global, double-blind, phase-III trial of 435 patients with advanced kidney cancer (renal cell carcinoma) who had either received no prior drug treatment or had received prior cytokine-based treatment. Patients were randomly assigned on a two to one basis to receive either pazopanib or placebo. Pazopanib reduced the risk of disease progression or death by 54 per cent (hazard ratio = 0.46 with 95 per cent confidence interval 0.34 to 0.62; P<0.0000001).1 The overall response rate in the pazopanib arm for the overall study population was 30 per cent with duration of response of 59 weeks.
The majority of adverse events were mild to moderate, the most common (incidence =20 per cent) being diarrhoea, hypertension, hair colour change, nausea, anorexia, and vomiting. The most common grade 3/4 adverse events (incidence >3 per cent) were diarrhoea (4 per cent), hypertension (4 per cent), and asthenia (3 per cent). The most common laboratory abnormalities (incidence =50 per cent) were elevated levels of liver enzymes known as transaminase, with elevated ALT as the most common grade 3/4 event (12 per cent). Investigator-reported serious adverse events included liver-related events (3 per cent), arterial thrombotic events (3 per cent) and haemorrhage (3 per cent). In this study, approximately 4 per cent of patients on treatment compared to 3 per cent of patients on placebo had a fatal event. Investigators attributed death due to study drug in approximately 1.4 per cent of patients in the treatment arm. Some of these adverse events/serious adverse events have been reported with this class of agents.
Pazopanib is an oral medicine that prevents the growth of new blood vessels to tumours. The growth of new blood vessels is a process called angiogenesis. All solid tumours need blood vessels to survive, and by stopping or slowing this process, medicines in this category may halt the progression of tumour growth.
In December 2008, GSK submitted a GSK new drug application (NDA) to the US Food and Drug Administration (FDA) and, in early 2009, a European marketing authorization application (MAA) to the European Medicines Agency (EMEA) for pazopanib for the treatment of advanced renal cell carcinoma (RCC) based on these data. The submission was recently accepted by the FDA. Pazopanib is not yet approved in any country for any indication at this time.
"We're extremely pleased to see the progress in developing pazopanib for advanced kidney cancer, but this represents just one type of cancer in need of new treatments. Our global studies using pazopanib are designed to find new ways to use a proven mechanism to fight a diverse group of cancers," said Paolo Paoletti, senior vice president, R&D Oncology Unit. "This further demonstrates our efforts to discover new medicines that provide tangible clinical benefits for patients."
Renal cell carcinoma (RCC) is the most common type of kidney cancer and accounts for approximately nine out of ten cases.