Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non–Small Cell Lung Cancer Haa-Na Song, MD,

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Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non–Small Cell Lung Cancer Haa-Na Song, MD,

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Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non–Small Cell Lung Cancer Haa-Na Song, MD, Ki Sun Jung, MD, Kwai Han Yoo, MD, Jinhyun Cho, MD, Ji Yun Lee, MD, Sung Hee Lim, MD, Hae Su Kim, MD, Jong-Mu Sun, MD, PhD, Se-Hoon Lee, MD, PhD, Jin Seok Ahn, MD, PhD, Keunchil Park, MD, PhD, Yoon-La Choi, MD, PhD, Woongyang Park, MD, PhD, Myung-Ju Ahn, MD, PhD Journal of Thoracic Oncology Volume 11, Issue 4, Pages e45-e47 (April 2016) DOI: 10.1016/j.jtho.2015.12.093 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Tissue obtained from the patient. (A) Tissue section from the patient's pleura showing metastatic adenocarcinoma; section was obtained when the disease was diagnosed (hematoxylin and eosin [HE] stain; magnification, ×200). (B) Tissue section from an axillary lymph node showing metastatic adenocarcinoma before HM61713 treatment (HE stain; magnification, ×100). (C) Tissue section from an axillary lymph node showing metastatic adenocarcinoma before HM61713 treatment (HE stain; magnification, ×200). (D) Tissue section from an axillary lymph node showing metastatic adenocarcinoma; section obtained after the patient had been receiving HM61713 for 17 months and her disease had progressed (HE stain; magnification, ×100). Journal of Thoracic Oncology 2016 11, e45-e47DOI: (10.1016/j.jtho.2015.12.093) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Computed tomography (CT) scans of the patient. (A) CT scan before HM61713 treatment. Primary mass in the left upper lobe and multiple pleural nodules in a mediastinal lymph node were observed. (B) CT scan after 6 months of HM61713 treatment. The extent of the primary tumor and mediastinal lymph node nodules was slightly decreased. (C) CT scan after 17 months of HM61713 treatment. Increased extent of primary tumor and multiple metastatic lymphadenopathies were noticed. (D) CT scan of the abdomen and pelvis after 17 cycles of HM61713 revealed peritoneal metastasis with a large amount of ascites and massive omental cake and extensive metastatic lymphadenopathy. Journal of Thoracic Oncology 2016 11, e45-e47DOI: (10.1016/j.jtho.2015.12.093) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 The next-generation sequencing readings from a post-HM61713 treatment tumor biopsy specimen. (A) A list of mutations in the sample. (B) The tumor sample shows C797S epidermal growth factor receptor gene (EGFR) mutation; the mutation is present at an allele frequency of 4%. (C) The T790M EGFR mutation is present at an allele frequency of 8%. (D) The sample also shows EGFR exon 19 deletion (in 19.3% of readings). Journal of Thoracic Oncology 2016 11, e45-e47DOI: (10.1016/j.jtho.2015.12.093) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions