GlaxoSmithKline announces Swiss approval of Tyverb®, a new oral treatment for advanced breast cancer

GlaxoSmithKline announced today an important milestone for advanced breast cancer patients across Europe with approval of the first oral ErbB1 and ErbB2 dual inhibitor, Tyverb® (lapatinib). Lapatinib, in combination with capecitabine, received approval from Switzerland’s regulatory authority,Swissmedic,for the treatment of patients with advanced ormetastatic breast cancer whose tumours overexpress ErbB2 (HER-2) and who have relapsed after, or not responded to, trastuzumab therapy.


Lapatinib is a small molecule that is administered orally and works by getting inside the cancer cell and inhibiting two receptor proteins — the tyrosine kinase components of ErbB1 and ErbB2 receptors, which are responsible for tumour growth. This innovative mechanism of action is a new way to treat breast cancer and is different from current targeted therapies for ErbB2 positive disease.


This approval was based on a pivotal Phase III trial (EGF100151) in women with advanced ormetastatic ErbB2 positive breast cancer whose disease had progressed following treatment with trastuzumab and other cancer therapies. The data showed that the median time to progression was 27.1 weeks on the combination of lapatinib and capecitabine versus 18.6 weeks on capecitabine alone (hazard ratio 0.57 (CI 0.43, 0.77) p=0.0001). The response rate was 23.7% versus 13.9% (p=0.017).[1]


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 majority of adverse events and laboratory abnormalities were mild to moderate in severity and were not significantly higher than those seen with capecitabine monotherapy.


"This is an extremely significant and exciting breakthrough for patients and physicians across Switzerland. Lapatinib offers patients an effective, well-tolerated treatment and as an oral therapy offers added convenience for patients. Lapatinib is now available in Switzerland and subject to regulatory approval we remain ontrack to launch lapatinib in the rest of Europe during the second half of 2007" said Paolo Paoletti, SVP and Global Head of the Oncology Medicine Development Centre at GSK. "The approval of lapatinib demonstrates our R&D organisation’s strong commitment to the discovery and development of novel cancer treatments. We are dedicated to the further study and development of lapatinib in a variety of settings including early breast cancer as well as in other types of cancer.”


Brain Metastases as Relapse Site

Brain metastases develop in one third of women with ErbB2 (HER-2) positive metastatic breast cancer, and 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 percent.[2]

In the Phase III trial on which the Swiss approval is based, preliminary results suggest that lapatinib may play a role in decreasing the development of brain metastases as site of first relapse. CNS relapse were lower in the lapatinib plus capecitabine arm versus the capecitabine alone arm.i Additional studies are ongoing in an effort to confirm this preliminary finding.

Future for Lapatinib - Ongoing Clinical Trials

Further studies are ongoing and are investigating the use of lapatinib either alone or in combination with other therapies for the treatment of breast cancer in women that are ErbB2 positive, including first-line in previously untreated metastatic breast cancer, as well as an adjuvant therapy for primary or 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.[3],,[4]


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.


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References:
[1] Tyverb® Prescribing Information. GSK data on file.

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

[3] 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.

[4] 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 ProceedingsPartI.Vol 24, No. 18S (June 20 Supplement) 2006: 4502.