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GlaxoSmithKline initiates trial of Tykerb (lapatinib) in patients with ErbB2-overexpressing breast cancer brain metastasis following Herceptin and cranial radiotherapy


SAN ANTONIO, December 9, 2005– GlaxoSmithKline (GSK) has announced the initiation of a global multicenter Phase II trial (known as EGF105084) to evaluate Tykerb (lapatinib) for the treatment of ErbB2-overexpressing (HER2+) breast cancer that has metastasized to the brain. Tykerb is an orally bioavailable small molecule which potently inhibits, two receptors, ErbB2 and ErbB1, and is currently in development as a first-line treatment for ErbB2-overexpressing breast cancer. Several centers, first in the USand then throughout the world, will begin enrolling patients with breast cancer who have progressive brain metastases following cranial radiotherapy and prior trastuzumab (Herceptin)-based therapy. Tykerb currently does not have regulatory approval for therapeutic use in any market.

Herceptin-based regimens have improved both systemic control and overall survival in patients with metastatic ErbB2 overexpressing breast cancer [Slamon, 2001; Cobleigh, 1999; Vogel, 2002; Burstein, 2001]. Herceptin, however, may not cross the blood-brain barrier and ErbB2-overexpressing breast cancer may have a predilection for metastases to visceral sites including the brain [Pestalozzi, 2000; Grossi, 2003, Stemmler, 2005]. As a result, central nervous system disease progression is emerging as a significant clinical problem in this patient population. Preliminary evidence of activity with Tykerb has been observed in ongoing clinical trials which have enrolled patients with ErbB2-overexpressing breast cancer brain metastases.

“This clinical trial, specifically in patients with brain metastases resulting from breast cancer, is unprecedented and underscores our continued dedication to discovering new treatment options for even the most difficult–to-treat malignancies,” said Paolo Paoletti, M.D., Senior Vice President of the OncologyMedicineDevelopmentCenter, at GSK. “The EGF105084 trial will investigate the therapeutic potential of Tykerb in addressing this significant unmet clinical need.”

The EGF105084 trial will enroll 220 patients to provide a more extensive analysis of safety and efficacy data in this setting. A similar population of patients was studied in a National Cancer Institute-sponsored study [Cancer Therapy Evaluation Program (CTEP) Trial 6969], and recently completed enrollment.

The EGF105084 trial is designed to assess the impact of Tykerb therapy by monitoring lesions in the brain using magnetic resonance imaging. A centralized radiological review will be conducted. Other treatment endpoints include reduction in tumor-related neurological symptoms, duration of response to therapy, time to progression at any site and overall survival.

Study participants will be separated into two cohorts:

* Patients able to carry out most daily activities(ECOG Performance Status 0-1) and who have received one or two prior Herceptin-containing regimens
* Patients ambulatory and capable of all self-care but unable to carry out any work activities,(ECOG Performance Status 2), or who have received more than two prior Herceptin-containing regimens

Few trials have examined the role of chemotherapy in the treatment of brain metastases from breast cancer and most studies of novel agents for breast cancer have specifically excluded patients with brain metastases.

Incidence of Brain Metastases from Breast Cancer

Approximately 20 percent of breast cancer patients with metastatic or stage IV disease are diagnosed with brain metastases, and autopsy data suggests a true incidence of nearly 30 percent. Retrospective analyses have disclosed a 28-43% incidence of brain metastases among women treated with Herceptin for stage IV ErbB2 overexpressing breast cancer across multiple institutions [Clayton, 2004; Bendell, 2003; Burstein, 2003; Weitzen, 2002; Wardley, 2002; Heinrich, 2003].

About Metastatic Breast Cancer

The World Health Organization reports that just over one million cases of breast cancer are diagnosed annually. Breast cancer is the most common non-cutaneous malignancy in women and one of the leading causes of cancer death.

Approximately 10 percent of newly diagnosed breast cancer patients have locally advanced and/or metastatic disease; 20 to 85 percent of patients (depending on initial stage, tumor biology, and treatment strategy) diagnosed with early breast cancer will develop recurrent and/or metastatic disease.2 The median survival time for women treated for metastatic breast cancer is two years.3

About Tykerb

Tykerb, a small molecule that can be administered orally, inhibits the tyrosine kinase components of ErbB1 and ErbB2 receptors. Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple processes involved in tumor progression, invasion, and metastasis. Overexpression of these receptors has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival. GSK is using advanced technologies, including pharmacogenetics, to better define patient populations that may respond to Tykerb.

Tykerb is an experimental drug that does not have regulatory approval in any country for any use outside of clinical trials. It is being developed by GSK as an orally administered therapy for breast cancer and other solid tumors.

About Tykerb Trials

Information about participating sites can be obtained by sending inquiries to the appropriate e-mail address below:

In North America,

In Europe,

In the rest of the world,

Information about this and other ongoing clinical trials of Tykerb in breast cancer can be obtained by visiting or calling 800-563-7137. Information is also available at, a Web site maintained by the USgovernment.

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

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the US 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 2004.

Notes to editors:

Tykerb is also designated as GW572016.

Herceptin® is a registered trademark of Genentech, Inc.


1 H.J. Stemmler et al. Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer. Breast. In press. 2005.

2 C. Bernard-Marty et al. Facts and Controversies in Treatment of Systemic Metastatic Breast Cancer. The Oncologist. 2004:9:617-632.

3 ibid.

4 A Khosla et al. Brain, Metastases., Feb. 2005.

5 B Felding-Habermann, Inhibition of Brain Metastases in Breast Cancer. California Breast Cancer Research Program Website. 2005.


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