Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic.

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Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance Zhen Wang, MD, PhD, Jin-Ji Yang, MD, Jie Huang, MD, PhD, Jun-Yi Ye, PhD, Xu-Chao Zhang, PhD, Hai-Yan Tu, MD, Han Han-Zhang, PhD, Yi-Long Wu, MD Journal of Thoracic Oncology Volume 12, Issue 11, Pages 1723-1727 (November 2017) DOI: 10.1016/j.jtho.2017.06.017 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Allelic context of EGFR T790M and C79S during combination treatment of first- and third-generation EGFR tyrosine kinase inhibitors. (A) After the development of resistance to osimertinib, circulating tumor DNA analysis revealed EGFR C797S (red) located in trans with T790M (green). (B) After the commencement of combination treatment of first- and third-generation EGFR tyrosine kinase inhibitors, partial response was achieved and accompanied by undetectable EGFR C797S. (C) At disease progression, EGFR C797S reemerged and was located in cis to T790M. Journal of Thoracic Oncology 2017 12, 1723-1727DOI: (10.1016/j.jtho.2017.06.017) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Clinical responses to osimertinib in combination with erlotinib. The patient achieved a partial response (PR) after 1 month of administration of osimertinib in combination with erlotinib. The response was confirmed 2 months later. He experienced progressive disease (PD) after 3 months. Red arrow indicates transhepatic biliary stent and red circles indicate target lesion in abdomen. Journal of Thoracic Oncology 2017 12, 1723-1727DOI: (10.1016/j.jtho.2017.06.017) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Dynamic monitoring of EGFR mutations during treatment with EGFR tyrosine kinase inhibitors. The dynamic changes in the allelic fraction of EGFR mutations were depicted. The y axis represents the allelic fraction, and the x axis represents treatment milestones. Each color represents a variant. PR, partial response; PD, progressive disease. Journal of Thoracic Oncology 2017 12, 1723-1727DOI: (10.1016/j.jtho.2017.06.017) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Clonal progression. Schematic diagram of clonal evolution of the patient, who carried EGFR 19 del before and during afatinib treatment. EGFR T790M subsequently developed at disease progression, and the patient was swicthed to osimertinib. At disease progression, development of EGFR T790M in trans with C797S occurred and the patient was switched to a combination of erlotinib and osimertinib. When the patient's disese progresssed again, circulating tumor DNA analysis revealed EGFR T790M in cis with C797S. Journal of Thoracic Oncology 2017 12, 1723-1727DOI: (10.1016/j.jtho.2017.06.017) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions