GSK presents phase lll data for lapatinib at San Antonio breast cancer symposium

Issued: London, UK

• Improvement in disease-free survival does not reach statistical significance in study of delayed adjuvant therapy with lapatinib (Tykerb or Tyverb) monotherapy in HER2 positive breast cancer.

Results from TEACH (Tykerb Evaluation After Chemotherapy) were presented today at the 2011 CRTC-AACR San Antonio Breast Cancer Symposium.  TEACH is a randomised, double-blind, placebo-controlled Phase III trial to evaluate the effects of lapatinib monotherapy when given to women who were diagnosed with HER2 positive breast cancer, received treatment excluding trastuzumab, and remained disease free.  The median time from diagnosis to study entry was 3 years. Use of lapatinib in the delayed adjuvant setting is investigational only and not approved by regulatory authorities anywhere in the world.  

The primary objective of the study was to compare disease-free survival (DFS) between women receiving lapatinib and those receiving placebo.  More than 3000 women who completed neo-adjuvant or adjuvant chemotherapy, did not receive trastuzumab and did not have evidence of disease were randomised to receive lapatinib or placebo for up to 12 months or until a DFS event, defined as objective disease recurrence, a second primary cancer, contralateral breast cancer  or death from any cause.  After a median follow up of 4 years, DFS events occurred in 13% of patients in the lapatinib arm and 17% of patients in the placebo arm of the trial (Hazard Ratio = 0.83 95% Confidence Interval, 0.70 to 1.00; stratified log-rank 2-sided p=0.053).  Therefore, although an improvement in disease-free survival in favor of lapatinib was observed, this result did not meet the prespecified criteria for statistical significance.

Serious adverse events were reported in 6% of the lapatinib arm and 5% of the placebo arm.  The rate of Grade 3 diarrhoea was 6% in the lapatinib arm and <1% in the placebo arm (no Grade 4 events).  The rate of Grade 3 rash was 5% in the lapatinib arm and <1% in the placebo arm.  There was one Grade 4 rash event in the lapatinib arm   Hepatobiliary adverse events of Grade 3/4 severity were reported in 2% of the lapatinib arm and <1% of the placebo arm.    

“Although we are disappointed that the improvement in disease-free survival with lapatinib monotherapy in TEACH did not reach statistical significance, lapatinib combination therapy remains an important treatment option for patients with metastatic Her2+ breast cancer whose disease has progressed on treatment with trastuzumab-based regimens,” said Rafael Amado, Senior Vice President Oncology Development.  “We look forward to the results from ongoing clinical trials with lapatinib in different combinations and lines of therapy, including the adjuvant setting, to assess the optimal use of lapatinib in women with HER2 positive breast cancer.”  

Lapatinib was first approved for use in combination therapy in the metastatic setting in 2007 and is currently approved in 107 countries including the U.S., Europe, Australia, India, Brazil, Russia, Turkey, South Korea and other countries around the world.  

About TEACH:  The TEACH trial (Tykerb Evaluation After CHemotherapy; EGF105485) is a Phase III,  randomised, double-blind, placebo-controlled, study of lapatinib versus placebo in women with HER2-positive breast cancer who have not been previously treated with trastuzumab.  Most (55%) of the patients did not receive treatment with trastuzumab because they had completed treatment before trastuzumab was available and it was not institutional practice to use trastuzumab in the delayed adjuvant setting.  22% of the women enrolled in TEACH did not have access to trastuzumab because it was not available in their country or investigative centre and the remaining women were not treated with trastuzumab due to other reasons, including patient preference/convenience.  HER2 status for study entry was initially determined by immunohistochemistry (IHC) testing or fluorescent in situ hybridization (FISH) at local laboratories or at a central laboratory if HER2 status was unknown locally.  All patients’ HER2 status was subsequently evaluated at a central laboratory using FISH.  The primary objective was to compare disease-free survival (DFS) between women treated with lapatinib and those treated with placebo in the early and delayed adjuvant treatment settings in a unique patient population.  TEACH was conducted in collaboration with Massachusetts General Hospital and more than 450 investigative centres in more than 30 countries participated in this study.  

About lapatinib (Tykerb or Tyverb)

In Europe, lapatinib, in combination with an aromatase inhibitor (AI), is indicated for the treatment of post-menopausal women with hormone receptor (HR)-positive, HER2 (ErbB2) over-expressing metastatic breast cancer and for whom chemotherapy is currently not intended.  In Europe, lapatinib is also approved in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumours over-express HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.  

In the United States, lapatinib is indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that over-expresses the HER2 receptor for whom hormonal therapy is indicated.  Lapatinib in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.  Lapatinib is also FDA approved in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumours over-express HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.  

US FDA boxed warning and important safety information for Tykerb

Hepatotoxicity has been observed in clinical trials and post marketing experience.  The hepatotoxicity may be severe and deaths have been reported.  Causality of the deaths is uncertain.  Patients with known severe hypersensitivity to TYKERB or any of its components should not take TYKERB.  Also, patients may experience decreased left ventricular ejection fraction, hepatotoxicity, diarrhoea, interstitial lung disease/pneumonitis, QT prolongation, and risk of fetal harm in pregnant women.  If TYKERB is to be administered to patients with severe hepatic impairment, dose reduction should be considered.  The most common adverse reactions during therapy with TYKERB plus letrozole compared to letrozole were diarrhoea, rash, nausea, and fatigue.  The most common adverse reactions during therapy with TYKERB plus capecitabine versus capecitabine alone were diarrhoea, palmar-plantar erythrodysesthesia, nausea, rash, vomiting, and fatigue.  

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GlaxoSmithKline cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, 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 GSK's operations are described under 'Risk Factors' in the 'Business Review' in the company's Annual Report on Form 20-F for 2010.