The U.S. Food and Drug Administration (FDA) has approved erlotinib tablets (Tarceva?; Genentech, Astellas Pharma), a once-daily, oral non-chemotherapy medicine for the initial or first-line treatment of people with metastatic non-small cell lung cancer (NSCLC) whose tumors have certain epidermal growth factor receptor (EGFR) activating mutations as detected by an FDA-approved test. In clinical trials erlotinib has shown to inhibit EGFR, a protein involved in the growth and development of cancers.

The FDA also approved the cobas? EGFR Mutation Test, which was developed by Roche and validated in the pivotal EURTAC (European Randomized Trial of Tarceva versus Chemotherapy)study. In the study, treatment with erlotinib demonstrated that patients lived longer without their disease getting worse (median progression-free survival [PFS] 10.4 months vs. 5.2 months; HR=0.34; p<0.001 [95% CI 0.23 to 0.49] compared to chemotherapy. The safety profile for erlotinib in this study was consistent with previous studies of the drug in NSCLC.

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2013, and NSCLC accounts for 85% of all lung cancers. It is estimated that approximately 60% of lung cancer diagnoses are made when the disease is in the advanced stages.

EGFR in Lung Cancer
EGFR is a protein that extends across the cell surface. 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 or 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.

Personalization: cobas EGFR Mutation Test
The cobas EGFR Mutation Test is a real-time, polymerase chain reaction-based diagnostic test for the qualitative detection and identification of exon 19 deletion or exon 21 (L858R) substitution mutations in the EGFR gene in DNA derived from formalin-fixed, paraffin-embedded tumor (FFPET) tissue from NSCLC patients. The test is intended to be used to identify patients with advanced NSCLC whose tumors harbor these certain types of mutations.

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?Ten to 30% of people worldwide with lung cancer have tumors that test positive for certain EGFR mutations,? noted Hal Barron, M.D., chief medical officer and head, Genentech Global Product Development. ?People with this type of lung cancer now have the option to use a personalized medicine as their initial treatment to help them live longer without their disease worsening.?

?With this approval, more patients across all lines of therapy have access to Tarceva,? commented Sef Kurstjens, M.D., chief medical officer, Astellas Pharma Inc. ?This new indication is emblematic of Astellas? commitment to continue our development efforts in lung cancer and precision medicine.?

?Increasingly, doctors and patients rely on diagnostics to help guide personalized treatment decisions. The approval of the cobas EGFR Mutation Test highlights the importance of sensitive, accurate tests that can be conducted in time to inform crucial treatment decisions,? explained Paul Brown, head of Roche Molecular Diagnostics.

In the United States, erlotinib is already approved, irrespective of histology or biomarker status for people with advanced-stage NSCLC whose cancer has not spread or grown after initial treatment with certain types of chemotherapy (maintenance treatment). erlotinib is also approved for patients with advanced-stage NSCLC whose cancer has spread or grown after receiving at least one chemotherapy regimen (second- or third-line treatment). However, erlotinib is not meant to be used at the same time as certain types of chemotherapy for advanced NSCLC.

First-line use
This latest FDA approval for erlotinib is based on the results of the Phase III EURTAC study, which evaluated the first-line use of erlotinib versus platinum-based chemotherapy in people with EGFR-activating mutation-positive advanced NSCLC. Tumor shrinkage (response rate) was observed in 65% of patients treated with erlotinib and 16% of patients treated with chemotherapy. The most frequent (greater than or equal to 30%) adverse events in erlotinib-treated patients were diarrhea, weakness, rash, cough, shortness of breath and decreased appetite. The most frequent Grade 3-4 reactions in erlotinib-treated patients were rash and diarrhea.

EURTAC was designed and sponsored by the Spanish Lung Cancer Group(SLCG) and conducted in Spain, France and Italy in cooperation with Roche. In the trial, the cobas EGFR Mutation Test was used to confirm people with mutations (exon 19 deletion or exon 21 [L858R] substitution) in the EGFR gene.From February 2007 to January 2011, 174 patients mostly of European descent were randomly assigned to receive erlotinib or platinum-based chemotherapy. The primary endpoint was investigator-assessed PFS. Randomization was stratified by certain EGFR mutations and ECOG performance status (0 vs. 1 vs. 2).

The safety profile for erlotinib in the EURTAC study was consistent with previous studies of erlotinib in NSCLC. The most frequent (greater than or equal to 30%) adverse events in erlotinib-treated patients were diarrhea, weakness, rash, cough, shortness of breath and decreased appetite. The most frequent Grade 3-4 reactions in Tarceva-treated patients were rash and diarrhea.

For more information:
– Full prescribing information

Clinical trial
NCT0044622 – 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

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