Results of Phase III EURTAC-study presented today shows that first-line use of erlotinib (Tarceva?, Genentech/Astellas Pharma) in Western patients with a genetically distinct type of advanced non-small cell lung cancer (NSCLC)nearly doubled the time people with NSCLC with EGFR activating mutations lived without their disease getting worse compared with chemotherapy. The median progression-free survival or PFS in patients treated with erlotinib was 9.7 months compared to 5.2 months with chemotherapy.
Erlotinib is approved for patients with advanced NSCLC whose cancer has not spread or grown after initial treatment with certain types of chemotherapy (maintenance treatment). The drug is also approved for patients with advanced NSCLC whose cancer has spread or grown after receiving at least one chemotherapy regimen (second-/third-line treatment).
EGFR in Lung 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. Binding leads to activation of the EGFR protein which triggers a complex signaling cascade inside the cell that leads to events including accelerated cell growth and division and development of metastases (tumor growth and spread to other parts of the body). Some NSCLC tumors have activating mutations in the EGFR gene, changing the structure of the EGFR proteins such that they have increased activity
In the study, erlotinib significantly reduced the risk of the disease ge.tting worse by 63% compared with standard chemotherapy (hazard ratio=0.37, p<0.0001). The safety profile for erlotinib was consistent with previous studies in NSCLC. These new data are being presented at the 47th Annual Meeting of the American Society of Clinical Oncology(ASCO) taking place in Chicago, June 3 to 7, 2011.
EURTAC Trial
The European Randomised Trial of Tarceva vs. Chemotherapy (EURTAC) was designed and sponsored by the Spanish Lung Cancer Group (SLCG), a multi-center, multidisciplinary cooperative working group, and conducted together with investigators from France and Italy in cooperation with Roche. As part of the study 1,275 patients were screened for EGFR activating mutations and 174 patients were randomly assigned to receive erlotinib or platinum-based chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included response, overall survival (OS) and toxicity profiles.
Genetically distinct
The genetically distinct type of lung cancer studied in EURTAC (epidermal growth factor receptor, or EGFR, activating mutation-positive NSCLC) occurs in approximately 10% of lung cancer patients in the Western population and approximately 30% of Asian patients. Similar results were observed in another Phase III trial (OPTIMAL) conducted in Asian patients with this form of NSCLC.
“Two studies have now shown that erlotinib as a first-line therapy for EGFR mutation-positive advanced lung cancer increased the time people lived without cancer worsening compared with standard chemotherapy,” said Hal Barron, M.D., chief medical officer and head, Global Product Development, Roche. “This is an important step forward in our goal of providing personalized options for people with advanced lung cancer.”
“We are pleased with the results from the EURTAC study, which is promising for patients with this genetically distinct type of NSCLC,” said Steve Ryder, president of Astellas Pharma Global Development. “The data from the EURTAC study reinforces the role that erlotinib may have in NSCLC patients with a once-a-day oral pill and a known toleration profile.”
Regulatory update
Roche has applied to the European Medicines Agency (EMA) to extend the current EU label for erlotinib to include first-line use in people with advanced EGFR activating mutation-positive NSCLC. Discussions are ongoing with the U.S. Food and Drug Administration (FDA) regarding a submission that will include the use of a companion diagnostic test to help identify patients with activating EGFR mutations who are appropriate candidates for erlotinib.
