An independent data monitoring committee has recommended that the phase III EURTAC study be stopped early because the study met its primary endpoint. At a planned interim analysis it was shown that compared to platinum-based chemotherapy erlotinib (Tarceva?, Roche/Genentech/OSI Oncology) significantly extended the time people with newly diagnosed advanced non small cell lung cancer (NSCLC) with EGFR (epidermal growth factor receptor) activating mutations lived without their disease getting worse (progression-free survival or PFS).

A preliminary safety analysis showed the safety profile was consistent with previous studies of erlotinib. The data will be submitted for presentation at a future medical meeting.

Epidermal growth factor and ling cancer
EGFR is a protein that extends across the cell membrane. The epidermal growth factor (EGF) binds to the part of the EGFR protein that sits on the outside of the cell. [1] Binding leads to activation of the EGFR protein which triggers a complex signalling cascade inside the cell that leads to events including accelerated cell growth and division and development of metastases (tumour growth and spread to other parts of the body).[2, 3] Some NSCLC tumours have activating mutations in the EGFR gene, changing the structure of the EGFR proteins such that they have increased activity.

The European Randomised Trial of Tarceva vs. Chemotherapy (EURTAC) which has been designed and sponsored by the Spanish Lung Cancer Group (SLCG), a multicenter, multidisciplinary cooperative working group based in 135 centres in Spain, and conducted together with investigators from France and Italy in cooperation with Roche is the first phase III study in a Western population with this distinct form of lung cancer. A similar study (OPTIMAL) has been carried out in an Asian population.

EURTAC is a prospective, randomised, controlled phase III trial evaluating the first-line use of erlotinib versus platinum-based chemotherapy in patients with advanced NSCLC with EGFR activating mutations. The primary end point of the study is progression free survival. Secondary endpoints include overall survival, one-year survival, objective response rate and safety profile. The platinum-based chemotherapy regimens used are cisplatin/gemcitabine; cisplatin/docetaxel; carboplatin/gemcitabine; and carboplatin/docetaxel.

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?The EURTAC study demonstrates that testing for EGFR activating mutations can identify people who may be candidates to receive Tarceva as their initial treatment for advanced lung cancer,? said Hal Barron M.D., Roche’s Chief Medical Officer and Head, Global Product Development. ?We are encouraged by these results and look forward to discussing them with health authorities around the world.?

In June 2010 Roche applied to the European Medicines Agency (EMA) to extend the current label for erlotinib to include the first-line treatment of people with advanced NSCLC whose tumours harbour EGFR activating mutations. Based on the EURTAC study data, OSI and Genentech plan to discuss similar updates to the erlotinib label with the U.S. Food and Drug Administration (FDA). Roche and OSI will also collaborate regarding submissions with other health authorities. Following approvals, identifying these people would give doctors the option to start erlotinib early with the aim of gaining maximum impact from its use. This approach of personalised healthcare opens up the prospect of further improving care. It is estimated that as many as one in ten (10%) lung cancer patients in the Western population and one in three (30%) Asian patients with lung cancer have NSCLC with EGFR activating mutations.[4,5]

Erlotinib is the only EGFR inhibitor approved by both the EMA and FDA for use after first-line treatment to help keep the disease process under control (maintenance therapy) and in the second-line setting for the treatment of patients with advanced or metastatic NSCLC irrespective of EGFR mutation status. The safety and efficacy profile of erlotinib is well characterised in both maintenance and second-line settings based on data from clinical studies and use in more than 400,000 patients worldwide.

[1] NCI Cancer Bulletin. Last accessed November 30 2010.
[2] Prenzel N et al. Endocrine-Related Cancer. (2001). 8:11?31. [3] Britten CD. Mol Cancer Ther; 2004. 3 1335-42.
[4] Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958?67
[5] Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol 2006;11:190?8

For more information:
Phase III Study (Tarceva?) vs Chemotherapy to Treat Advanced Non-Small Cell Lung Cancer (NSCLC) in Patients With Mutations in the TK Domain of EGFR
Erlotinib Versus Gemcitabine/Carboplatin in Chemo-naive Stage IIIB/IV Non-Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Exon 19 or 21 Mutation (ML20981)

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