Primary And Acquired Resistance To Egfr Tkis

Although the use of gefitinib and erlotinib in the setting of EGFR-driven cancers has revealed some clinical efficacy, these agents are limited in their beneficial scope. If one examines NSCLC as a representative model for targeting EGFR activity, the overall response rate of patients to gefitinib or erlotinib in published studies is approximately 10% in unselected NSCLC patients in U.S. and European populations. For patients harboring EGFR-activating mutations, the rate of response is between 78% and 100% (69).

Approximately 90% of NSCLC patients with advanced metastatic disease exhibit little or no response to the drugs, a phenomenon referred to as primary or de novo resistance, since it is inherent to the genotypic profile of the patient prior to treatment and does not develop due to selective pressures imposed by the drug. This latter situation is representative of acquired resistance, and will be discussed below.

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