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Treatment of EGFR T790M-Positive Non-Small Cell Lung Cancer

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Abstract

The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic mutations of the epidermal growth factor receptor (EGFR). Despite remarkable initial responses, patients eventually develop progressive disease, with the most common cause of resistance to first-line EGFR TKIs being the acquired T790M mutation. Various third-generation EGFR TKIs have been developed to specifically target this acquired mutation, of which osimertinib is currently the only approved agent. In addition, the eagerly anticipated data from the FLAURA study recently found improved efficacy with increased progression-free survival (PFS) with osimertinib compared to standard of care first-generation EGFR TKIs in the first-line setting. Of note, osimertinib has also demonstrated promising efficacy in patients with known brain metastases. However, as patients invariably develop resistance during treatment with osimertinib, most commonly with the development of triple mutated EGFR (sensitizing mutations/T790M/C797S), which is resistant to all existing EGFR TKIs, efforts are currently ongoing to develop new strategies or novel compounds to specifically target this resistance mechanism.

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Authors and Affiliations

  1. Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore, 119228, Singapore

    Joan Rou-En Choo, Chee-Seng Tan & Ross A. Soo

  2. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Ross A. Soo

  3. School of Surgery, The University of Western Australia, Perth, Australia

    Ross A. Soo

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Ross Soo has received honoraria from AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Taiho, and a research grant from AstraZeneca.

Chee-Seng Tan has received honoraria from AstraZeneca, Merck, Boehringer Ingelheim, Novartis, Eli Lilly, Eisai, and Bristol-Myers Squibb.

Joan Choo declares no conflict of interests.

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Choo, J.RE., Tan, CS. & Soo, R.A. Treatment of EGFR T790M-Positive Non-Small Cell Lung Cancer. Targ Oncol 13, 141–156 (2018). https://doi.org/10.1007/s11523-018-0554-5

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