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Better Survival in Lung Cancer Patients with EGFR


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Gene Mutations

According to a study published in the Journal of Clinical Oncology, non-small cell lung cancer (NSCLC) patients with a mutation in the EGFR gene may survive longer than patients without an EGFR mutation. It is not clear, however, whether EGFR mutation status can be used to guide treatment decisions.

Lung cancer remains the leading cause of cancer-related mortality in the United States and Europe. NSCLC refers to the type of cell in which the cancer originated. It accounts for approximately 75% to 80% of all lung cancers. While the mainstay of treatment for metastatic NSCLC is chemotherapy, researchers are exploring new drugs and new combinations of drugs in hopes of finding more effective treatments.

One of the newer treatments for NSCLC is Tarceva™ (erlotinib). Tarceva is an epidermal growth factor receptor (EGFR) inhibitor. EGFRs are small proteins that are found on the surface of all cells. EGFR binds proteins circulating in the blood called growth factors. The binding action between EGFR and growth factors stimulates biological processes within the cell to promote growth of a cell in a strictly controlled manner. However, in many cancer cells, EGFR is either abundantly over-expressed or the EGFR biological processes that normally stimulate cell growth are constantly active. This leads to the uncontrolled and excessive growth of the cancer cell. Tarceva is currently approved by the FDA for the treatment of advanced NSCLC in patients who have received at least one prior therapeutic regimen.

Response to Tarceva and other drugs may be influenced by mutations in specific genes. If gene mutations are found to predict response to treatment, information about a patient’s genetic status may help doctors select the best treatment for that patient. Two genes that may influence response to treatment for NSCLC are EGFR (the gene that produces the protein EGFR) and KRAS. In order to assess how mutations in these two genes influence survival and response to treatment, researchers evaluated 274 previously untreated stage IIIB or stage IV NSCLC patients. Patients received first-line treatment with the chemotherapy drugs carboplatin and paclitaxel, either alone or in combination with Tarceva.

Thirteen percent of patients had a mutation in the EGFR gene. Patients with an EGFR mutation survived longer than patients without an EGFR mutation, regardless of treatment group. There was no strong evidence that patients with an EGFR mutation were more likely to respond to Tarceva than patients without an EGFR mutation.

Twenty-one percent of patients had a mutation in the KRAS gene. Among patients with a KRAS mutation, treatment with chemotherapy and Tarceva appeared to shorten survival compared to treatment with chemotherapy alone.

The researchers conclude that although EGFR mutation status may provide important information about the prognosis of a patient with NSCLC, it is still not clear whether EGFR mutation status can be used to guide decisions about treatment with Tarceva. The reason for the worse survival among patients with a KRAS mutation and treatment with Tarceva is unclear. The researchers suggest caution in interpreting this result.

Patients with NSCLC may wish to talk with their doctor about the risks and benfits of participating in a clinical trial further evaluating Tarceva or other therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com.

Reference: Eberhard DA, Johnson BE, Amler LC et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Journal of Clinical Oncology. 2005;23:5900-5909.

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