GlaxoSmithKline Reports Positive New and Updated Data on Tyverb (lapatinib) at the 14th European Cancer Conference (ECCO)

BARCELONA, 25th September 2007 : GlaxoSmithKline today announced, for the first time in Europe, positive data from two key studies on Tyverb® (lapatinib).  Results from study EGF30001 show that lapatinib in combination with paclitaxel demonstrates clinical activity in previously untreated patients with metastatic ErbB2 (HER2) positive breast cancer[i].  Updated efficacy results from study EGF100151 confirm previously demonstrated clinical benefits in improved time to progression (TTP) with use of lapatinib plus capecitabine versus capecitabine alone.[ii]  Preliminary genetic analysis data from this study also suggest a correlation between elevated ErbB2 expression and response to lapatinib plus capecitabine treatment.2 Lapatinib is the first oral, small molecule, dual targeted therapy that works intracellularly (from inside the cell) to inhibit both ErbB1 (EGFR) and ErbB2 (HER2).

“Both studies presented here today add to the growing body of evidence showing the potential for lapatinib to directly impact clinical practice in the treatment of ErbB2-positive metastatic breast cancer,” said Professor John Crown, Consultant Medical Oncologist, St. Vincent's University Hospital, Dublin and a leading investigator for the EGF100151 trial. “Importantly, these data demonstrate how lapatinib in combination with certain standard chemotherapies may benefit patients in different clinical settings, including first-line treatment.  Lapatinib has also demonstrated activity in particularly difficult to treat patient populations, such as those who develop secondary brain (CNS) metastases.  In addition, analysing tumour tissue samples to understand the genetics of how the cancer develops and responds to treatment is tremendously exciting, and warrants continued investigation.”

Biomarker analysis of lapatinib with paclitaxel versus paclitaxel as first-line treatment in 580 patients with metastatic breast cancer.  (Abstract 2097, embargoed until Tuesday 25th September 2007, 09:15 CET)

This trial evaluated lapatinib with paclitaxel versus paclitaxel plus placebo as first-line treatment for patients with metastatic breast cancer (MBC).  In this Phase III, randomised, multicentre, prospective trial, 580 patients whose ErbB2 status was unknown or negative at study entry were stratified via metastatic site. Initial study results confirmed that there was a direct correlation between lapatinib efficacy and ErbB2 overexpression.

Biomarkers were correlated with clinical efficacy in 579 out of 580 patients and 91 patients (18%) were retrospectively determined to be ErbB2 positive.1  In this patient subset, a statistically significant improvement was observed in the lapatinib plus paclitaxel group versus placebo plus paclitaxel treated patients:

  • Median progression-free survival (PFS): 34.4 versus 22.6 weeks (p=0.007)
  • Median TTP: 35.1 versus 25.1 weeks (p=0.0107)
  • Complete or partial response occurred in 60% of patients versus 36% (p=0.027)

In ErbB2-negative disease, combination therapy did not demonstrate an incremental benefit for patients.

The most common adverse events (AEs) included rash, diarrhoea, nausea, vomiting, neutropenia and mucositis.  The addition of lapatinib to paclitaxel resulted in an increased incidence of diarrhoea and rash.  Serious adverse event related deaths were higher in the combination arm (2.7% vs. 0.6%).  

Lapatinib plus capecitabine in HER2-positive advanced breast cancer: Report of updated efficacy and gene-array data. (Abstract 2096, embargoed until Tuesday 25th September 2007, 09:00 CET)

This trial (EGF100151) evaluated lapatinib with capecitabine versus capecitabine alone for patients with advanced or metastatic ErbB2-positive breast cancer whose disease had progressed following treatment with trastuzumab and other cancer therapies.

Results from the trial confirmed the previously demonstrated benefit of lapatinib in combination with capecitabine versus capecitabine alone, and also provided evidence for statistically significant systemic anti-ErbB2 therapy effects on the development of brain metastases:2

  • Median TTP: 27 weeks versus 19 weeks (p=0.00013)
  • Overall response rate (ORR): 24% versus 14% (p=0.017)
  • Progression in brain metastases: 2% versus 11% (p=0.0445)

The data suggests that patients whose tumours overexpress ErbB2 gain greater clinical benefit from treatment with lapatinib plus capecitabine.

Brain metastases develop in up to a third of women with ErbB2-positive MBC[iii] and this is an area of significant unmet medical need.  Once the disease advances to this site overall prognosis is poor with the average one-year survival estimated at about 20%.[iv]

The most common adverse events during therapy with lapatinib plus capecitabine were gastrointestinal (diarrhoea, nausea and vomiting) or skin toxicities (hand and foot syndrome and rash). The addition of lapatinib to capecitabine resulted in an increased incidence of diarrhoea and rash, however the majority of the reported events were grade 1 or 2 in severity.

“We are delighted to have two consecutive Phase III presentations on lapatinib at this meeting. Both data sets support the potential for lapatinib to be an important component of treatment regimens for women with ErbB2 positive breast cancer, whether previously treated or not,” said Paolo Paoletti, M.D., Senior Vice President of the Oncology Medicine Development Center at GSK. “GSK’s ongoing clinical programme will evaluate lapatinib both as a monotherapy and in combination with a variety of other agents across the spectrum of ErbB2-positive breast cancer, from metastatic to early breast cancer.”

Future for lapatinib - Ongoing Clinical Trials

The comprehensive clinical development programme is evaluating lapatinib both alone and in combination with other therapies (chemotherapy, hormonal therapy, other targeted agents and VEGF inhibitors) across the spectrum of ErbB2-positive breast cancer, from metastatic to early breast cancer.  Trials are also ongoing in a range of other solid tumours that overexpress ErbB1 and/or ErbB2, including head & neck and renal cell cancer.[v],[vi]

GSK in Oncology   
GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary “bench to bedside” approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes partnerships with more than 160 cancer centres. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.

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.

Notes to editors:

Tyverb® and Tykerb® are registered trademarks of the GlaxoSmithKline group of companies.

Tykerb® is the brand name used for lapatinib in the United States and certain other countries.

Tyverb® is the brand name used for lapatinib in Switzerland and is the proposed trade name in the European Union, pending regulatory approval.

Lapatinib is approved for sale in the United States, Australia, New Zealand, Switzerland, South Korea and certain countries in South America and the Middle East.

Registration dossiers for lapatinib have been filed in the European Union, Canada, and a number of countries in Asia, Latin America and the Middle East.

To access the latest GSK Oncology materials visit www.gskcancermedia.com

REFERENCES


[i] Finn et al.  Abstract # 2097 – Biomarker analysis of lapatinib with paclitaxel versus paclitaxel as a first line treatment in 580 patients with metastatic breast cancer. Presented at the 14th ECCO conference 2007.

[ii] Crown et al.  Abstract # 2096 – Lapatinib plus capecitabine in HER2+ advanced breast cancer (ABC): report of updated efficacy and gene-array data

[iii] Bendell et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 2003;97(12):2972-7

[iv] Mahmoud-Ahmed et al. Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study.  Int J Radiat Oncol Biol Phys 2002;54:810-7

[v] El-Hariry, I., Harrington K. et al.  A phase I, open label study (EGF100262) of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).  Oral presentation, 1st International Meeting on Innovative Approaches in Head & Neck Oncology, Barcelona, Spain. 22nd - 24th February 2007

[vi] Ravaud A, Gardner, R. Hawkins H et al. Efficacy of lapatinib in patients with high Tumour EGFR expression: Results of a phase III trial in advanced renal cell carcinoma (RCC). Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement) 2006: 4502.


Posted: September 2007

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