Healthcare Industry News:  TYKERB 

Biopharmaceuticals Oncology

 News Release - June 4, 2007

GSK's Pazopanib Shows Positive Results in Patients With Advanced Renal Cell Carcinoma, Ovarian Cancer and Soft Tissue Sarcoma

CHICAGO, June 4 (HSMN NewsFeed) -- GlaxoSmithKline (LSE and NYSE: GSK News) today announced results from ongoing Phase II studies of pazopanib in advanced or metastatic renal cell carcinoma (RCC), ovarian cancer and soft tissue sarcoma (STS). These trials were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The results observed in these trials with pazopanib support further investigations.

Pazopanib is an oral, investigational angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit, important proteins in the angiogenic process. Angiogenesis, which is the growth of new blood vessels in the body, plays a critical role in the growth and spread of tumors. (1,2)

Renal cell carcinoma study (Abstract 5031) (3)

This ongoing Phase II randomized discontinuation study is evaluating patients with advanced or metastatic RCC who have not received prior systemic therapy or have failed one prior therapy (cytokine or bevacizumab-containing regimen). All patients received 800 mg of pazopanib taken orally, once-daily during a 12 week lead-in period. Based on data available on 60 patients at the time of a planned interim analysis, the Independent Data Monitoring Committee (IDMC) recommended that randomization to placebo for patients with stable disease should be discontinued. The study continued as an open-label, single- arm study with all patients receiving pazopanib.

The preliminary week 12 response rate for all 225 patients was 27%. In addition, stable disease was achieved in 46% of patients for a total disease control rate of 73%. Responses have been observed beyond week 12, and the overall response rate will be reported at study completion. Response was determined according to RECIST (Response Evaluation Criteria In Solid Tumors) which is a set of published rules that defines when cancer patients improve (respond), stay the same (stable), or worsen (progress) during treatments. Almost half of the enrolled patients remain in the study.

"These results with pazopanib are very encouraging," said lead investigator Dr. Thomas Hutson, Baylor Sammons/Texas Oncology PA, Dallas, Texas. "The high response rates seen so far in this study show clear clinical activity in advanced or metastatic renal cell carcinoma, and a number of ongoing studies also demonstrate therapeutic promise in several other tumor types."

The most frequent adverse events (AEs) were diarrhea, fatigue, hair color change, nausea, and hypertension. Pazopanib had a low incidence of hand-foot syndrome (10%), rash (12%), hemorrhage (9%), and mucositis (5%). Please see safety considerations below.

The incidence of RCC is rising throughout the world (4) with 208,000 new cases diagnosed annually. (5) Although patients with early-stage disease can potentially be cured with surgery, many will either experience a recurrence after surgery or have advanced or metastatic disease at the time of initial presentation. (6)

RCC is generally resistant to standard chemotherapy, (7) and immunotherapeutic regimens using recombinant human interleukin-2 (IL-2) and recombinant human interferon a-2b (IFN-a), either alone or in combination, have been widely used in patients with advanced disease. Although high-dose IL-2 has shown promise with durable complete remissions observed in 7% of patients, toxicity has limited its widespread use. (8) Lower dose cytokine therapies have not shown the same magnitude of response and are also limited by their toxicity. (8) Recently, several anti-angiogenesis drugs, including sunitinib, sorafenib and bevacizumab have demonstrated clinical activity in patients with advanced or metastatic RCC. (8) Although targeted therapies have advanced the treatment of advanced or metastatic RCC, complete and durable responses are not achieved in the majority of patients (8) and a need remains for new treatment options.

"These results clearly demonstrate the potential pazopanib offers as a future therapeutic option not only in renal cell cancer, but across many different tumor types," said Debasish Roychowdhury, MD, Vice President, Global Clinical Development, Oncology Medicine Development Centre, GSK. "The broad clinical development program for pazopanib, in various cancers as monotherapy and in combination therapy, including combinations with TYKERB, underscores our continued commitment to delivering effective new treatments for patients with cancer."

Ovarian cancer study (Abstract 5561) (9)

This ongoing Phase II open-label, monotherapy study is evaluating pazopanib in patients with cancer of the ovary, fallopian tube or peritoneum, who have failed standard platinum-based therapy. Treatment is continued until disease progression, withdrawal due to AEs, or withdrawal of consent. Biological activity (measured as a decrease in CA-125, a biologic marker of clinical activity) was seen in nine (41%) of 22 evaluable patients with relapsed disease. The most common AEs were diarrhea, nausea, abdominal pain, fatigue, and vomiting. Please see safety considerations below.

Globally, ovarian cancer (204,000 cases and 125,000 deaths) is the sixth most common cancer and the seventh most common cause of death from cancer in women. (5) The majority of patients with ovarian cancer will have advanced disease at the time of initial diagnosis. Typically, these patients are managed with surgery followed by combination chemotherapy. Although the majority of patients will respond initially to firstline therapy, recurrent disease remains a considerable problem. (10)

Soft tissue sarcoma study (Abstract 10031) (11)

STS is a disease in which malignant cancer cells begin growing in soft tissues, such as muscles, tendons, connective tissues, fat, blood vessels, nerves, and tissues around joints. This ongoing Phase II study is evaluating the effect of pazopanib in patients with advanced STS who have failed prior therapy for advanced disease. Currently there is no standard treatment for such patients. (12) Of 80 patients included in the first stage of this study, 27 (34%) achieved progression-free survival at 12 weeks.

Pazopanib was evaluated in four types of STS in the first stage of the study: leiomyosarcoma, liposarcoma, synovial sarcoma and other soft tissue sarcomas. Pazopanib demonstrated activity in all tumor types except liposarcoma, and the study is ongoing to further investigate activity in the responsive tumor types. The most common AEs recorded were hypertension, fatigue, hair color change, and nausea. Please see safety considerations below.

About pazopanib

Pazopanib is an investigational, oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-kit. Pazopanib is currently in Phase III development for the treatment of advanced or metastatic RCC, after completing patient enrollment several months ahead of schedule, and is also being studied in a number of other trials across various tumor types.

Safety Considerations

In more than 1000 patients treated to date with pazopanib in clinical trials, serious but uncommon (<1%) reports of bowel perforation, myocardial infarction/angina and cerebrovascular accidents/transient ischemic attacks have been reported. The most common laboratory abnormality was an elevation in liver transaminase which occurred as an asymptomatic, reversible event.

About GlaxoSmithKline

GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and healthcare companies -- is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at http://www.gsk.com.

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2006.

Notes to editors: TYKERB is a registered trademark of the GlaxoSmithKline group of companies in the United States. To access the latest GSK Oncology media materials, visit http://www.gsk.com

References:

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

(2) Jain RK. Antiangiogenic therapy for cancer: current and emerging concepts. Oncology. 2005 Apr;19(4 Suppl 3):7-16

(3) Hutson, T. E., Davis I. D., et al. Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): interim results of a phase II randomized discontinuation trial (RDT). Presented at the 2007 ASCO Annual Meeting, Chicago, USA Abstract number 5031.

(4) Murai, M. and Oya, M. Renal cell carcinoma: etiology, incidence and epidemiology. Curr. Opin. Urol. 2004;14, 229-233.

(5) Parkin, M., Bray F. et al. Global Cancer Statistics. CA Cancer J Clin. 2005;55:74-108

(6) VEG102616 study protocol

(7) Motzer, R.J. and P. Russo, Systemic therapy for renal cell carcinoma. J. Urol. 2000; 163:408-417.

(8) Garcia, JA., Rini B. Recent progress in the management of advanced renal cell carcinoma. CA Cancer J Clin. 2007 Mar- Apr;57(2):112-25.

(9) Friedlander, M., et al. Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: initial results of a Phase II study. Presented at the 2007 ASCO Annual Meeting, Chicago, USA Abstract number 5561

(10) VEG104450 study protocol

(11) Sleiffer, S. et al. A Phase II study of pazopanib (GW786034) in patients with relapsed or refractory soft tissue sarcoma (STS): an EORTC soft tissue and bone sarcoma group study (EORTC62043). Presented at the 2007 ASCO Annual Meeting, Chicago, USA Abstract number 10031

(12) EORTC protocol 62043


Source: GlaxoSmithKline

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