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EGFR Mutant

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Molecular Targeted Therapy of Lung Cancer

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Abstract

Before 2009, advanced non-small cell lung cancer (NSCLC) was regarded as a single disease entity, which was treated by cytotoxic chemotherapy and provided a response rate of 20–35 % and a median survival time (MST) of 10–12 months. In 2004, it was found that activating mutations of the epidermal growth factor receptor gene (EGFR) were present in a subset of NSCLCs and that tumors with EGFR mutations were highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Four phase III studies (NEJ 002, WJTOG3405, OPTIMAL, and EUROTAC) have opened the possibility of precision medicine for advanced NSCLC. These studies prospectively compared a TKI of gefitinib or erlotinib with cytotoxic chemotherapies as the first-line therapy in NSCLC harboring EGFR mutations. They reported that progression-free survival (PFS) as the primary endpoint was significantly longer with TKIs than with the standard chemotherapies (hazard ratios = 0.16–0.49). Although these studies indicated identical overall survival between the treatments, quality of life (QoL) was maintained for longer by patients treated with gefitinib in NEJ 002. Therefore, TKIs should be considered as the standard first-line therapy for advanced EGFR-mutated NSCLCs. Since 2009, a new step has been introduced to the treatment algorithm for advanced NSCLC. In this chapter, both the road to precision medicine for advanced NSCLC and the present knowledge of new-generation TKIs (afatinib or third-generation TKIs) and of TKIs in combination treatments are reviewed.

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  1. Department of Respiratory Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Kunihiko Kobayashi & Hiroshi Kagamu

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  1. Kunihiko Kobayashi
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  2. Hiroshi Kagamu
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Correspondence to Kunihiko Kobayashi .

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  1. Department of Medical Oncology Graduate School of Medicine, Chiba University, Chiba, Japan

    Yuichi Takiguchi

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Kobayashi, K., Kagamu, H. (2017). EGFR Mutant. In: Takiguchi, Y. (eds) Molecular Targeted Therapy of Lung Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-10-2002-5_10

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