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Last Updated: 01/27/2017

Evaluating the Predictive and Prognostic Value of Molecular Markers to the Epidermal Growth Factor Receptor in a Phase III Study of Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

The DCTD’s Cancer Therapy Evaluation Program (CTEP) has led a major effort by NCI, the Food and Drug Administration (FDA), and the Centers for Medicare and Medicaid (CMS) to develop a national clinical trial for non-small cell lung cancer (NSCLC) to validate a predictive marker for therapies targeted to the epidermal growth factor receptor (EGFR). The study is currently in late phase development and is expected to be activated in mid-2008.

Both erlotinib and pemetrexed are approved second-line treatments for advanced NSCLC and are currently being tested in different first-line and adjuvant settings. EGFR inhibition may be more effective in a selected, rather than an unselected, population. In several studies, retrospective analyses of subsets of patients have recognized molecular and/or clinical features associated with increased probability of response to EGFR inhibition. These features include EGFR gene copy number or protein expression, mutational status, proteomics profile, adenocarcinoma histology, female gender, Asian ethnicity, and smoking status. However, no prospective study has been performed to definitively address this issue. With the current available information, it is still not clear which, if any, EGFR-related marker will accurately predict a population that will benefit from EGFR inhibition.

The study, known as N0723, is an intergroup phase III study that will be led by the North Central Cancer Treatment Group and is designed to prospectively determine whether patients with advanced lung cancer and with high or low EGFR copy number have differences in outcome when treated with the tyrosine kinase inhibitor erlotinib or the chemotherapeutic agent pemetrexed, in the second-line setting. It is hypothesized that erlotinib will be superior in the patients with EGFR-positive lung cancer, whereas pemetrexed would be favored in the patients with EGFR-negative lung cancer. In addition, the study will incorporate pharmacogenetic studies for both erlotinib and pemetrexed that will be important to further identify patients with different sensitivity and toxicity profiles to these therapies.

This study will attempt to prospectively and definitively establish the value of selecting the treatment patient population based on the presence or absence of a tumor molecular marker in the patient. The study will try to answer questions regarding the predictive and prognostic value of EGFR molecular markers, as well as correlations with clinical features. Approximately 1,200 patients will be tested for the presence or absence of the marker, and the treatment populations will be randomized based on the outcome. Both EGFR-positive or EGFR-negative patients will receive either erlotinib or pemetrexed.

About the Director

James Doroshow James H. Doroshow, M.D., FACP, has been the Director of the Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), National Institutes of Health (NIH), since 2004. He is responsible for integrating the activities of DCTD with NCI’s other divisions and offices, as well as extramural scientists and clinicians, patient advocates, and professional cancer organizations. More…