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Biopharmaceuticals Oncology

 News Release - June 3, 2006

GlaxoSmithKline Reports Positive New Data on Tykerb(R) (Lapatinib Ditosylate)

Pivotal Phase III trial showed that Tykerb nearly doubles time to progression for patients with ErbB2 (HER2) positive advanced breast cancer(1)

Tykerb demonstrates preliminary activity in brain metastases associated with breast cancer, an area of significant unmet medical need(2)

Tykerb shows activity in relapsed inflammatory breast cancer(3), a severely aggressive form of breast cancer

ATLANTA, June 3 (HSMN NewsFeed) -- GlaxoSmithKline plc (NYSE: GSK ; LSE: GSK ) today announced late-breaking results from a large, randomized, pivotal Phase III study of its small molecule dual kinase inhibitor, Tykerb® (lapatinib ditosylate). In this study, the combination of Tykerb and capecitabine (Xeloda®) versus capecitabine alone nearly doubled time to progression (36.9 weeks [8.5 months] in the combination arm versus 19.7 weeks [4.5 months] with capecitabine alone, p=0.00032) in women with refractory advanced or metastatic ErbB2 positive breast cancer whose disease had progressed following treatment with trastuzumab (Herceptin®) and other cancer therapies.(1) In April 2006, GSK stopped enrollment of the study based on the unanimous recommendation of an Independent Data Monitoring Committee (IDMC) because it had met its primary endpoint of time to disease progression, and exceeded the predetermined stopping criteria outlined in the committee charter.

Tykerb is an investigational drug and is not yet approved for marketing by any regulatory body.

Results of this, and several other important Tykerb studies, are being presented today at the 2006 American Society of Clinical Oncology (ASCO) annual meeting in Atlanta, Georgia. GSK plans to file for regulatory approval of Tykerb in the United States and Europe in the second half of 2006.

"Because ErbB2 positive breast cancer may eventually progress during or following treatment with trastuzumab, there has been a need for an effective alternative treatment that can successfully block the function of ErbB2 in another way," said Charles Geyer, M.D., Director of Breast Medical Oncology at Allegheny General Hospital (Pittsburgh, Pennsylvania) and principal investigator for this trial. "These results indicate that lapatinib [Tykerb] can provide a needed alternative when trastuzumab no longer appears to be helping to control the disease."

Tykerb, a small molecule that is 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 metastases. Overexpression of these receptors has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival.

"These results suggest that Tykerb has significant potential as an essential component of the treatment regimen for women with advanced breast cancer," said Paolo Paoletti, M.D., Senior Vice President of the Oncology Medicine Development Center at GSK. "Worldwide, more than one million women are diagnosed with breast cancer every year and it is a leading cause of cancer related deaths. The data presented at ASCO clearly demonstrates GSK's continued commitment to changing the treatment paradigm for these women, in hopes of one day making cancer a chronic disease."

The international, multicenter, open-label study (EGF100151) enrolled 392 patients who had advanced or metastatic breast cancer with documented ErbB2 overexpression and whose disease progressed following treatment with trastuzumab and other cancer therapies. The interim analysis included 321 patients (160 in the Tykerb-capecitabine arm and 161 in the capecitabine monotherapy arm).(1)

Adverse events (AEs) leading to discontinuation were similar in the Tykerb-capecitabine combination arm (14 percent) versus capecitabine alone (11 percent), as were overall AEs. AEs in the Tykerb-capecitabine arm included diarrhea, hand-foot syndrome and rash. An asymptomatic relative decrease of greater than or equal to 20 percent in left ventricular ejection fraction (LVEF), a measure of the strength of the heart observed through electrocardiogram, occurred in 2.5 percent of patients on the combination arm and less than 1 percent of patients on capecitabine; all patients recovered normal LVEF.

Another abstract being presented on June 4th (Abstract #583) shows a low incidence of cardiac events in patients treated with Tykerb. Results of an analysis of cardiac function in women treated with Tykerb in all trials to date showed that 37 of 2,812 women (1.3 percent) who have received Tykerb have experienced a decrease in LVEF (33 events were asymptomatic and 4 were symptomatic).

Tykerb Activity in Brain Metastases Associated with Breast Cancer

Treatment for brain metastases is an area of significant unmet medical need as one-third of women with ErbB2 overexpression and metastatic breast cancer develop central nervous system (CNS) or brain metastases. Once the disease advances to this stage, overall disease prognosis is poor with the average one-year survival from diagnosis estimated at about 20 percent.(4) Additional analysis from the EGF100151 study (Late-Breaking Abstract) suggests that Tykerb may play a role in decreasing the occurrence of brain metastases. Indeed, in the interim analysis, only 4 patients experienced CNS relapse in the Tykerb-capecitabine arm versus 11 in the capecitabine alone arm.(1)

Another study (abstract #503) being presented today at ASCO provides preliminary evidence suggesting that Tykerb may be effective in treating brain metastases associated with breast cancer. The Phase II trial was conducted by investigators at the Dana-Farber/Harvard Cancer Center, the University of North Carolina, and Georgetown University and was sponsored by the National Cancer Institute's Cancer Therapeutic Evaluation Program (CTEP). The trial evaluated Tykerb in 39 patients with ErbB2 positive breast cancer who had developed CNS metastases while on trastuzumab. As reported in the abstract, two patients achieved partial response as measured by RECIST, a linear measure of solid tumors. An additional five patients achieved stable disease for greater than or equal to 16 weeks. Volumetric analysis, which is a more precise three dimensional measure of tumor volume, was performed in 20 patients. Eight of the patients (40 percent) showed volumetric decline in CNS lesions - five patients showed greater than or equal to 30 percent volumetric decline and an additional three patients showed 15-30 percent volumetric decline. Although the trial did not demonstrate the hypothesized level of activity as assessed by RECIST, the study concludes that there is sufficient evidence of preliminary clinical effect to suggest that Tykerb can penetrate the CNS.(2) The most common adverse events with Tykerb were diarrhea (grade 3, 21 percent), fatigue (grade 3, 16 percent), and rash (grade 3, 5 percent).

Following the encouraging results from the CTEP trial, Tykerb is now being studied by GSK in a large, international, randomized Phase II study designed

to assess the impact of Tykerb monotherapy on brain metastases by monitoring lesions in the brain using Magnetic Resonance Imaging, a volumetric measure.

Inflammatory Breast Cancer

Inflammatory Breast Cancer (IBC) is an especially aggressive and devastating form of breast cancer that is associated with severe side effects and extremely poor prognosis. IBC occurs when breast cancer cells block the lymph vessels in the breast skin and it generally spreads quickly to other parts of the body. Women with IBC live an average of about three years after diagnosis.(5)

Another trial presented today (Abstract #502) at ASCO evaluated Tykerb, as a single agent in patients with relapsed or refractory IBC. In this study, 57 patients were assigned to one of two groups. The first group were ErbB2 overexpressors and the second were ErbB2 non-overexpressors. Both groups received daily Tykerb treatment. The analysis presented showed that 62 percent of patients who were ErbB2 overexpressors, had a clinical response to Tykerb (15 out of 24).(3)

In this trial, Tykerb was generally well tolerated. The majority of side effects associated with Tykerb were grade 1/2 skin and gastrointestinal.

Initiation of Tykerb Expanded Access Program

Although Tykerb is an investigational drug and is not yet approved for marketing by any regulatory body, GSK recognizes that at this stage in the development program, physicians may wish to consider treating certain patients with Tykerb based on clinical evidence to date. Therefore, after discussion and agreement with the FDA, GSK announced today that it will open a global Expanded Access Program (EAP) for Tykerb in combination with capecitabine. GSK is currently enrolling sites to participate in the program.

Advanced or metastatic breast cancer patients may be eligible for the EAP if they have previously received therapies including anthracycline, taxane and trastuzumab and are not enrolled in or eligible for another Tykerb clinical trial. For more information regarding qualification and enrollment in the U.S. and additional details on the Tykerb EAP, beginning June 12th please call: 1- 888-4TYKERB (489-5372). Outside the U.S., physicians should email: and patients should speak directly to their doctor about eligibility.

About Tykerb

Tykerb is being developed by GSK as an orally administered therapy for breast cancer and other solid tumors. GSK is using advanced technologies, including pharmacogenetics, to better define patient populations that may respond to Tykerb.

GSK plans to submit Tykerb regulatory filings in the U.S. and Europe in the second half of 2006. The compound already has been granted Fast Track status by the FDA for the treatment of refractory advanced or metastatic breast cancer in women who have documented ErbB2 overexpression and who have failed previous therapy.

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 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 2005.

Notes to editors:

Tykerb is also designated as GW572016.

Tykerb is a registered trademark of the GlaxoSmithKline group of companies in the United States and Europe.

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


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(1) Late breaking clinical trial presented at The 2006 ASCO Annual Meeting, 3 June 2006.

(2) Abstract #503 - Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer.

(3) Abstract #502 - EGF103009, a Phase II trial of lapatinib monotherapy in patients with relapsed/refractory inflammatory breast cancer (IBC): Clinical activity and biologic predictors of response.

(4) R. Weil et al. Breast Cancer Metastasis to the Central Nervous System. American Journal of Pathology. 2005;167:913-920.

(5) National Cancer Institute.

Source: GlaxoSmithKline

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