Rare and Classic EGFR Mutations in NSCLC Have Distinct Responses to Therapy, According To New Study

Rare and Classic EGFR Mutations in NSCLC Have Distinct Responses to Therapy, According To New Study

shutterstock_150725585Lung cancer is divided in two major groups: small-cell lung cancer and non-small cell lung cancer (NSCLC), with prognosis for NSCLC patients still rated as very poor. Although improvements have been made to enhance surgery efficacy, irradiation and chemotherapy treatments for the disease, healthcare professionals indicate an urgent need to identify new targets for the treatment of non-small cell lung cancer.

In lung carcinoma, the most common (“classic”) mutations in epidermal growth factor receptor (EGFR) are positive prognostic markers for EGFR tyrosine kinase inhibitors (TKIs) therapy. However, in some cases there are rare EGFR mutations with unknown epidemiology, prognosis, and response to TKIs. Mutations within the EGFR gene are the most common therapeutically-targeted genomic modifications in NSCLC and lead to an oncogenic EGFR protein, which can be inhibited by EGFR TKIs.

A new study on this issue entitled “Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma” was published in the Journal of Thoracic Oncology by Dr. Zoltan Lohinai, first author, and led by Drs. Balazs Dome and Balazs Less Hegedus, co-senior authors from the Department of Thoracic Surgery at the Medical University of Vienna, along with colleagues.

In the study, the research team found that the majority of rare EGFR mutations were associated with smoking, decreased overall survival and lower response to EGFR tyrosine kinase inhibitors (TKIs) therapy when compared to the most common EGFR mutations.

Drs. Dome and Hegedus explained in a news release that their “study clearly demonstrates that rare and classic EGFR mutations show distinct epidemiological features and have different impacts on disease outcome and TKI therapy response.”

Based on their findings, the team concluded that it is crucial to perform studies that characterize EGFR tyrosine kinase inhibitors’ sensitizing effect of rare mutations for each patient, preventing the exclusion of patients with rare EGFR mutations that are sensitized to anti-EGFR therapy.

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