Research demonstrates differing genetic makeup of lung cancer in African-American patients

Cartoon diagram of the epidermal growth factor receptor (EGFR) (rainbow colored, N-terminus = blue, C-terminus = red) complexed with its ligand epidermal growth factor (magenta) based on the PDB 1NQL crystallographic coordinates.

Informs clinical development of EGFR inhibitor drugs The tumors of African-American non-small cell lung cancer patients are more likely to carry a higher number of copies of the epidermal growth factor receptor (EGFR) gene and fewer mutations of EGFR itself than Caucasians according to a study presented at the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology, cosponsored by ASTRO, ASCO, IASLC and the University of Chicago.

These genetic factors have been shown to predict long-term outcome and tumor responses when taking erlotinib and gefitinib – common EGFR inhibitor drugs.

Previous studies have determined that ethnicity can have an influence on the risk and outcome of non-small cell lung cancer patients, with African-American patients experiencing a higher risk and poorer outcomes. Ethnic background can also impact the genetic make-up and responsiveness of non-small cell lung cancer to EGFR gene blocking drugs. For example, a large number of Asian patients carry mutations of the EGFR gene than Caucasians, which can determine the likelihood of major clinical responses to EGFR inhibitor drugs while a higher copy number of EGFR is a predictor of better long-term outcome with the use of these drugs.

Researchers at the Departments of Medicine, Pathology and Biostatistics at Case Western Reserve University in Cleveland; the Departments of Medicine and Pathology at the University of Colorado Cancer Center in Aurora, Colo.; and the Instituto Clinico Humanitas IRCCS in Rozzano, Italy, sought to determine the frequency of EGFR abnormalities in African American patients since there is a paucity of data on this population.

The study authors observed 53 African-American patients with resected non-small cell lung cancer and found few EGFR mutations and an increase in the frequency of tumors with a high copy number of the EGFR gene. Previous studies have shown that an increase in the number of copies, regardless of mutation, predicts a better outcome with EGFR inhibitor drugs.

"The findings of this study were surprising since it was not expected that drug-sensitizing EGFR mutations would be so rare in this patient population," Rom Leidner, M.D., one of the study's authors and a clinical fellow in hematology/oncology at Case Western Reserve University said. "African-American patients remain underrepresented in clinical studies in oncology and therefore our knowledge base about how to modify our treatment strategies for this patient population remains poorly defined."

Researchers hope that the findings of their study could impact how clinical studies are designed in the future and how EGFR-targeted agents are used in the future. ###

The abstract, "A Study of Genetic Abnormalities of the EGFR Pathway in African American Patients with Non-Small Cell Lung Cancer," will be presented in a poster discussion session Friday, November 14, 2008 from 9:30 a.m. to 10:00 a.m. To speak to Dr. Leidner, please call Beth Bukata or Nicole Napoli on November 13-14, 2008, in the Press Room at the Chicago Marriott at 312-595-3177. You may also e-mail them at bethb@astro.org or nicolen@astro.org.

Contact: Beth Bukata bethb@astro.org 703-839-7332 American Society for Therapeutic Radiology and Oncology

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