GSK's Pazopanib Significantly Delayed Tumour Progression In Patients With Advanced Kidney Cancer

Main Category: Cancer / Oncology
Also Included In: Urology / Nephrology
Article Date: 04 Jun 2009 - 3:00 PDT

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Today, GlaxoSmithKline (GSK) announced the results of a Phase III study demonstrating that pazopanib reduced the risk of tumour progression or death by 54% compared to placebo.1

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.1 Patients who had previously received cytokine-based treatment showed 7.4 months of median PFS with pazopanib versus 4.2 months with placebo.1 These results were featured in an oral presentation at the annual American Society for Clinical Oncology (ASCO) meeting in Orlando, Florida.2

"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 Forlanini Hospitals, 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 2-to-1 basis to receive either pazopanib or placebo. Pazopanib reduced the risk of disease progression or death by 54% (hazard ratio = 0.46 with 95% confidence interval 0.34 to 0.62; P<0.0000001). The overall response rate in the pazopanib arm for the overall study population was 30% with duration of response of 59 weeks.

The majority of adverse events were mild to moderate, the most common (incidence ≥20%) being diarrhoea, hypertension, hair colour change, nausea, anorexia, and vomiting. The most common grade 3/4 adverse events (incidence >3%) were diarrhoea (4%), hypertension (4%), and asthenia (3%). The most common laboratory abnormalities (incidence ≥50%) were elevated levels of liver enzymes known as transaminase, with elevated ALT as the most common grade 3/4 event (12%).1 Investigator-reported serious adverse events included liver-related events (3%), arterial thrombotic events (3%) and haemorrhage (3%).4 In this study, approximately 4% of patients on treatment compared to 3% of patients on placebo had a fatal event. Investigators attributed death due to study drug in 1.38% of patients in the treatment arm.1 Some of these adverse events have been reported with this class of agents.5

Pazopanib is an oral medicine that prevents the growth of new blood vessels to tumours.6 The growth of new blood vessels is a process called angiogenesis.7 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.7

In early 2009, GSK submitted a GSK new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and a European marketing authorisation 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, GSK Oncology R&D Unit. "This further demonstrates our efforts to discover new medicines that provide tangible clinical benefits for patients."

About RCC

Renal cell carcinoma (RCC) is the most common type of kidney cancer and accounts for approximately nine out of ten cases.8 In 2002, an estimated 208,000 new cases of kidney cancer were diagnosed globally.9

About Pazopanib and Clinical Development

Pazopanib has a broad clinical programme across multiple tumour types, with study details available at http://www.clinicaltrials.gov. Programmes currently underway in advanced RCC include a head-to-head comparison trial with sunitinib in patients with no prior drug treatment. More than 2,000 patients have been treated to date in clinical trials.

GSK is dedicated to developing effective treatment options for oncology patients. GSK has a pipeline and portfolio of fundamental and innovative medicines seen across the industry.

. References

1. Sternberg C, et al. Abstract #5021 - A Randomized, Double-blind Phase III Study of Pazopanib in Treatment-naive and Cytokine-pretreated Patients with Advanced Renal Cell Carcinoma (RCC). To be presented orally at the 2009 American Society of Clinical Oncology annual meeting.

2. NCI. Dictionary of Cancer Terms. "Progression Free Survival." Available at: http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=44782 Accessed April 21, 2009.

3. ASCO. 2009 Meeting Planner. "pazopanib." Available at: http://meetingplanner.asco.org/. Accessed April 21, 2009.

4. Data on file, GSK

5. Hutson, T, Figlin, R, Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies. The Oncologist. 2008; 13: 1084-1096.

6. Sonpavde, G. and Hutson, T. Pazopanib: A Novel Multitargeted Tyrosine Kinase Inhibitor. Curr Oncol Rep. 2007;Mar9(2):115-9.

7. American Cancer Society. What is Anti-Angiogenesis Treatment? Available here. Accessed April 21, 2009.

8. American Cancer Society. "What is Kidney Cancer (Adult) - Renal Cell Carcinoma?" Available here . Accessed April 21, 2009.

9. Parkin M, Bray F et al. Global Cancer Statistics. CA Cancer J Clin. 2002;55:74-108.

Source
GlaxoSmithKline