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EGFR Tyrosine Kinase Inhibitors: Difference in Efficacy and Resistance

  • Lung Cancer (T Mekhail, Section Editor)
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Abstract

Lung cancer will be diagnosed in 230,000 patients in the U.S. in 2013. Adenocarcinoma will be the most common histology, and 10 % of lung cancers will be diagnosed in never or former light smokers. These patients will be those most likely to harbor targetable mutations, in particular, mutations in epidermal growth factor (EGFR). Preclinical work beginning in the 1980s led to the development of EGFR-targeted therapy in lung cancer patients. Analysis of the responders to gefitinib and erlotinib led to the discovery of activating mutations underlying sensitivity to EGFR-directed treatment. Although EGFR-mutant patients have higher response rates, better quality of life, and longer progression free survival, all patients eventually develop resistance. Mutations in the tyrosine kinase domain that render tumors resistant to erlotinib and gefitinib are the most common mechanism of resistance. A second generation of EGFR inhibitors are now making their way to the clinic, with hopes of thwarting these resistance mechanisms or providing more durable responses via irreversible inhibition, as well as targeting of additional HER receptors. Here we review the evolution of EGFR as a target in lung cancer, and the second generation of EGFR inhibitors in development.

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Kyle W. Robinson declares no potential conflict of interest.

Alan B. Sandler has been a consultant to Genentech/Roche, Lilly, Pfizer, Celgene, and Gilead, provided expert testimony for Genentech/Roche and Pfizer, and served on speakers’ bureaus for Genentech/Roche, Lilly, Celgene, and Pfizer.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Oregon Health and Science University, 3181 SW Sam Jackson Park Road, MC: L586, Portland, OR, 97239, USA

    Kyle W. Robinson & Alan B. Sandler

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Correspondence to Alan B. Sandler.

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Robinson, K.W., Sandler, A.B. EGFR Tyrosine Kinase Inhibitors: Difference in Efficacy and Resistance. Curr Oncol Rep 15, 396–404 (2013). https://doi.org/10.1007/s11912-013-0323-7

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