PRESS RELEASE: GlaxoSmithKline announces data on Tykerb ® (lapatinib) plus capecitabine for the treatment of HER2-positive brea

GlaxoSmithKline announces data on Tykerb ® (lapatinib) plus capecitabine for the treatment of HER2-positive breast cancer brain metastases

Data on abstract 6076 embargoed until Sunday 16 December 2007, 13.00 pm GMT, 07:00 AM CST

Study shows TYKERB combination reduced the size of brain tumours associated with HER2-positive breast cancer

GlaxoSmithKline announced today results from the extension arm of a Phase II study on its first-in-class, oral small molecule HER2 (ErbB2) kinase inhibitor, TYKERB®(lapatinib). In this study of 49 patients, the combination of TYKERB plus capecitabine (Xeloda®) showed a reduction in HER2-positive breast cancer that had spread to the brain and had progressed on TYKERB alone1. Specifically, 20 per cent of patients who received TYKERB plus capecitabine experienced at least a 50 per cent volumetric reduction in measurable brain metastases; 37 per cent of patients experienced a volumetric decrease that was greater than or equal to 20 per cent. Additional data from this trial are included below. This is important because up to one-third of women with HER2-positive metastatic breast cancer may develop brain metastases during the course of their disease2. Results of this and other important TYKERB studies are being presented at the 2007 San Antonio Breast Cancer Symposium in San Antonio, TX.

“As women live longer with advanced breast cancer, some are developing brain metastases that are getting worse despite standard treatments, such as radiation,” said Nancy U. Lin, M.D., lead investigator and Instructor in Medicine, Dana-Farber Cancer Institute . “Very few medications have shown activity in the treatment of brain metastases, in particular HER2-positive metastatic breast cancer patients and therefore, these data are quite encouraging.”

TYKERB, in combination with capecitabine, is approved in the United States for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane and trastuzumab (Herceptin®)3. Additional studies are underway to learn the full potential of TYKERB for the prevention and treatment of brain metastases.

“I know first hand that HER2-positive breast cancer can have unique, difficult-to-treat complications. Brain metastases can be particularly devastating for patients, as they may cause blurred vision, speech impairments and can limit patients’ ability to engage in even simple day-to-day activities,” said Christine Druther, MSPH, founder and president, HER2 Support Group. “We look forward to the results of any and all research in the treatment of HER2-positive breast cancer and its complications.”

Data presented on abstract 60761

In this study, the combination of TYKERB plus capecitabine showed a reduction in HER2-positive breast cancer that had spread to the brain and had progressed on TYKERB alone. Preliminary results are available from the initial 49 patients who enrolled in the TYKERB plus capecitabine extension arm as of March 2007. Exploratory analysis revealed 18 patients (37 per cent) experienced at least a 20 per cent volume reduction in brain metastases, without progression of their disease outside of the brain, increase in steroid requirements or worsening of neurological signs or symptoms, and a median reduction in brain metastases of 4.8 cm3. Of these 18 patients, 10 patients (20 per cent) experienced at least a 50 per cent volume reduction in brain metastases with a median reduction in brain metastases of 7.1 cm3. As of September 2007, three patients remained on the parent study with TYKERB monotherapy and of the 51 patients enrolled in the extension arm with TYKERB plus capecitabine, eight remained on lapatinib plus capecitabine.

Of the 51 patients enrolled in the extension arm, 10 (20 per cent) who received TYKERB plus capecitabine experienced a partial response and 20 patients (39 per cent) achieved stable disease. The disease progressed in fifteen patients (29 per cent) who received the combination. The status of 6 patients (12 per cent) was unknown at the time of reporting.

The most commonly reported Grade 1/2 adverse events include hand-foot syndrome (palmar-plantar eryrthrodysaesthesia) (37 per cent), diarrhea (34 per cent), nausea (22 per cent), vomiting (12 per cent), anorexia (12 per cent), and nail disorder (12 per cent). The most common Grade 3 adverse events include hand-foot syndrome (8 per cent), nausea (8 per cent), vomiting (6 per cent), diarrhea (4 per cent) and fatigue (2 per cent).

“This trial and theongoing clinical development program for TYKERB represent GSK Oncology’s commitment to developing treatments that help improve the lives of cancer patients,” said Paolo Paoletti, M.D., Senior Vice President of the Oncology Medicine Development Center at GSK. “We plan to further study the effects of TYKERB in HER2-positive patients with brain metastases.”

Brain metastases associated with HER2-positive breast cancer

Metastatic breast cancer is the second most common type of cancer to develop brain metastases4. Approximately 10 per cent of newly diagnosed breast cancer patients have locally advanced and/or metastatic disease; 20 to 85 per cent of patients (depending on initial stage, tumor biology, and treatment strategy) diagnosed with early breast cancer will develop recurrent and/or metastatic disease5. Up to one-third of women with HER2-positive breast cancer may develop brain metastases2.

 

About Tykerb/TYVERB3

TYKERB/TYVERB (lapatinib) is a first-in-class oral small-molecule inhibitor of the HER2 (ErbB2) tyrosine kinase receptor. Stimulation of HER2 is associated with cell proliferation and with multiple processes involved in tumor progression and metastases. Over-expression of this receptor has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival. On March 13, 2007, the United States Food and Drug Administration (FDA) approved TYKERB, in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

TYVERB has been approved in more than 15 countries, and marketing applications for TYKERB/TYVERB have been filed around the world.

Important safety information*

As with other therapies for HER2 overexpression, Tykerb has been associated with reports of decreases in left ventricular ejection fraction (LVEF). Caution should be taken if Tykerb is to be administered to patients with pre-existing cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure. LVEF should be evaluated in all patients prior to and during treatment with Tykerb.

A dose reduction should be considered for patients with severe hepatic impairment.

Diarrhea was the most common adverse event resulting in discontinuation of study medication. Proactive management of diarrhea with anti-diarrheal agents is important, and severe cases of diarrhea may require administration of oral or intravenous electrolytes and fluids and interruption or discontinuation of therapy with Tykerb.

Tykerb has been associated with interstitial lung disease and pneumonitis. Discontinue Tykerb if patients experience severe pulmonary symptoms.*

Tykerb prolongs the QT interval in some patients. Consider ECG and electrolyte monitoring.

Fetal harm can occur when administered to a pregnant woman. Women should be advised not to become pregnant when taking Tykerb.

The most common adverse events (>20 per cent) during treatment with Tykerb plus capecitabine were diarrhea, vomiting, nausea, fatigue, palmar-plantar erythrodysethesia, and rash.

*Please see full prescribing information.

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 www.gsk.com [1].

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 'Business Review' in the company's Annual Report on Form 20-F for 2006.

Note to editors

TYKERB® is a registered trademark of the GlaxoSmithKline group of companies in the United States.

TYVERB® is a registered trademark of the GlaxoSmithKline group of companies in Europeand is the proposed trade name in certain markets, pending regulatory approval.

Herceptin®is a registered trademark of Genentech, Inc. in the U.S.and Roche Pharmaceuticals in Europe.

Xeloda®is a registered trademark of Roche Pharmaceuticals.

To access the latest GSK Oncology media materials, visit www.gsk.com/media [2].