Two Cases of Small Cell Lung Cancer Transformation from EGFR Mutant Adenocarcinoma During AZD9291 Treatment Jun Soo Ham, MD, Seokhwi Kim, MD, Hee Kyung.

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Two Cases of Small Cell Lung Cancer Transformation from EGFR Mutant Adenocarcinoma During AZD9291 Treatment Jun Soo Ham, MD, Seokhwi Kim, MD, Hee Kyung Kim, MD, Seonggyu Byeon, 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, Joungho Han, MD, PhD, Woongyang Park, MD, PhD, Myung-Ju Ahn, MD, PhD Journal of Thoracic Oncology Volume 11, Issue 1, Pages e1-e4 (January 2016) DOI: 10.1016/j.jtho.2015.09.013 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 (A) Tissue section from the pleura of the patient in case 1 (hematoxylin and eosin stain, magnification ×400) that was obtained before AZD9291 treatment and shows metastatic adenocarcinoma. (B) Tissue section obtained from a lung of the patient in case 1 and showing small cell carcinoma (hematoxylin and eosin stain, magnification ×400). (C) Tissue sample from the same lung (CD56 immunohistochemical stain, magnification ×400); CD56-positive staining was obtained when the patient's disease progressed while she was receiving AZD9291 for 14 months. (D) Tissue section from a lung of the patient in case 2 (hematoxylin and eosin stain, magnification ×400) that was obtained before AZD9291 treatment and shows adenocarcinoma. (E) Tissue section from a lung of the patient in case 2 showing small cell carcinoma (hematoxylin and eosin stain, magnification ×400). (F) Tissue section from the same lung (CD56 immunohistochemical stain, magnification ×400); CD56-positive staining was obtained when the patient's disease progressed while she was being given AZD9291 for 18 months. Journal of Thoracic Oncology 2016 11, e1-e4DOI: (10.1016/j.jtho.2015.09.013) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 In case 1, a next-generation sequence showed persistence of the L858R mutation (B) but loss of the T790M mutation (A). In case 2, a next-generation sequence showed persistence of the exon 19 deletion (C) but loss of the T790M mutation (A). Journal of Thoracic Oncology 2016 11, e1-e4DOI: (10.1016/j.jtho.2015.09.013) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Computed tomography (CT) scans of the patient in case 1. (A) CT scan before AZD9291 treatment. Multiple pleural nodules and a para-aortic lymph node were noted. (B) CT scan after 2 months of AZD9291 treatment. The extent of the pleural nodules and para-aortic lymph node was decreased. (C) CT scan after 14 months of AZD9291 treatment. A huge left upper lobe and hilar masses were noted. (D) CT scan after two cycles of etoposide and carboplatin chemotherapy. The huge masses were markedly smaller. Journal of Thoracic Oncology 2016 11, e1-e4DOI: (10.1016/j.jtho.2015.09.013) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Supplemental Figure 1 Computed tomography (CT) scans of the patient in case 2. (A) CT scan before AZD9291 treatment. Multiple lung nodules and masses were noted. (B) CT scan after 2 months of AZD9291 treatment. The extent of the multiple lung nodules and masses was decreased. (C) CT scan after 18 months of AZD9291 treatment. The multiple lung nodules were increased. (D) CT scan after three cycles of etoposide and carboplatin chemotherapy. The multiple nodules were markedly decreased. Journal of Thoracic Oncology 2016 11, e1-e4DOI: (10.1016/j.jtho.2015.09.013) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

Supplemental Figure 2 Next-generation sequences (NGS) of the patients in case 1 and case 2. (A) In case 1, NGS showed persistence of the L858R mutation and EGFR gene amplification. In case 2, NGS showed persistence of the exon 19 deletion. (B) In case 1, EGFR gene amplification was noted. (C) There were no abnormalities of retinoblastoma (RB) genes in either case. Journal of Thoracic Oncology 2016 11, e1-e4DOI: (10.1016/j.jtho.2015.09.013) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions