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EGFR mutations and molecularly targeted therapy: a new era in the treatment of lung cancer

Nature Clinical Practice Oncology volume 3, pages 170–171 (2006)Cite this article

Extensive preclinical data firmly established that many cancers, including non-small-cell lung cancer (NSCLC), frequently overexpress the epidermal growth factor receptor (EGFR), and that activation of the EGFR tyrosine kinase produces a number of downstream effects (including proliferation, invasion, metastasis, and inhibition of apoptosis) that are critically involved in a cell's acquisition of the malignant phenotype. Interruption of this signaling with a variety of EGFR inhibitors has been shown to decrease tumor cell viability, prevent proliferation, or both, in vitro and in vivo.

The orally active selective EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib were the first EGFR-targeted agents to be studied in patients with NSCLC. In phase II trials of gefitinib in patients with pretreated metastatic NSCLC, objective tumor response rates of 9–19% were seen in those receiving TKIs, and approximately 40% of patients showed improvement of symptoms.1,2 In a randomized, double-blind, phase III trial, erlotinib improved objective tumor response rate (8.9% versus 1%; P <0.001) and median survival time (6.7 months versus 4.7 months; P <0.001) in comparison with placebo in 731 patients with refractory metastatic NSCLC (the NCIC CTG BR.21 trial).3 A similarly designed trial examined the efficacy of gefitinib versus placebo in 1,692 patients with previously treated advanced NSCLC (the ISEL trial). While the overall survival for the entire group was not improved with gefitinib, preplanned subgroup analyses showed significantly longer survival with gefitinib in patients who had never smoked and in patients of Asian origin.4

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Acknowledgements

Grant support: lung cancer SPORE P50CA70907

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Authors and Affiliations

  1. Internal Medicine at the University of Texas Southwestern Medical Center and serves as the Chief of Hematology/Oncology at the Dallas VA Medical Center, Dallas, TX, USA

    Jonathan E Dowell

  2. Internal Medicine and Pharmacology, Director of the Hamon Center for Therapeutic Oncology Research and the Moncrief Center for Cancer Genetics, and a NCI Special Program of Research Excellence at the University of Texas Southwestern Medical Center, Dallas, TX, USA

    John D Minna

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Correspondence to John D Minna.

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Competing interests

JE Dowell is on a speakers bureau for Genentech and receives research funding from Genentech. JD Minna receives research support from AstraZeneca and ImClone.

Supplementary information

Supplementary Table 1

EGFR mutation frequencies in specific clinical subsets of non-small-cell lung cancer patients based on a compilation of the published data.

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Dowell, J., Minna, J. EGFR mutations and molecularly targeted therapy: a new era in the treatment of lung cancer. Nat Rev Clin Oncol 3, 170–171 (2006). https://doi.org/10.1038/ncponc0476

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