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Strategy on Patients with EGFR Mutation

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New Therapeutic Strategies in Lung Cancers

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Abstract

The use of EGFR TKIs in patients harboring classical EGFR mutations results in response rates (ORR), median progression-free survival (PFS), and overall survival in the order of 70 %, 12 months, and 2 years, respectively. First-line treatment is preferred as ORR, PFS, and quality of life are improved compared to chemotherapy. Gefitinib and erlotinib are referred to as first-generation EGFR TKIs. The second-generation TKIs afatinib and dacomitinib exhibit irreversible binding to ATP and inhibit multiple receptors of the ErbB/HER receptor family. Studies evaluating their potential superiority over first-generation TKIs are underway. All patients eventually develop resistance. A minority are primary resistant, i.e., not responding and progressing within 3 months. Possible mechanisms include resistance mutations (e.g., exon 20 insertions or T790M mutations), coexisting genetic alterations (e.g., KRAS mutations, MET amplification), or germline alteration of proapoptotic proteins. Secondary resistance is mediated by T790M mutation in 50–60 % of cases. Further mechanisms are alternative pathway activation and kinase switching or histologic transformation. New treatment options in acquired resistance are rapidly evolving. However, premature termination of EGFR TKI should be avoided as it may lead to “disease flare.” Early clinical phase I/II studies with third-generation EGFR TKIs, which selectively bind sensitizing as well as T790M resistance mutations, showed encouraging response rates of 28–64 %. Adjuvant EGFR TKI therapy may lead to increased disease-free survival, but results of further studies need to be awaited.

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Authors and Affiliations

  1. Departement Innere Medizin, Kantonsspital St. Gallen, Fachbereich Onkologie/Hämatologie, St. Gallen, 9007, Switzerland

    Martin Früh

  2. Department of Medical Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, China

    Qing Zhou

  3. Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China

    Linda Leung & Tony Mok

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  2. Qing Zhou
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Correspondence to Martin Früh .

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  1. Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    Solange Peters

  2. Pathologie thoracique, Institut Gustave Roussy, Villejuif, France

    Benjamin Besse

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Früh, M., Zhou, Q., Leung, L., Mok, T. (2015). Strategy on Patients with EGFR Mutation. In: Peters, S., Besse, B. (eds) New Therapeutic Strategies in Lung Cancers. Springer, Cham. https://doi.org/10.1007/978-3-319-06062-0_9

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