Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions Nathan D. Gay, MD, Ying Wang, MD, Carol Beadling, PhD, Andrea Warrick,

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Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions Nathan D. Gay, MD, Ying Wang, MD, Carol Beadling, PhD, Andrea Warrick, MSc, Tanaya Neff, MSc, Christopher L. Corless, MD, PhD, Khaled Tolba, MD Journal of Thoracic Oncology Volume 12, Issue 8, Pages e107-e110 (August 2017) DOI: 10.1016/j.jtho.2017.04.025 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 (A and B): Hematoxylin and eosin–stained sections (one from each case) showing invasive adenocarcinoma. Focal mucin production is evident in (B) (lower right). Journal of Thoracic Oncology 2017 12, e107-e110DOI: (10.1016/j.jtho.2017.04.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Contrast-enhanced computed tomography scans of the chest in case 1 showing a significant decrease in the large speculated right lower lobe mass and persistent response at 8 months after initiation of afatinib. Journal of Thoracic Oncology 2017 12, e107-e110DOI: (10.1016/j.jtho.2017.04.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Contrast-enhanced T1-weighted magnetic resonance imaging scan of the brain in case 1 showing a decrease in frontotemporal osseous metastasis. Journal of Thoracic Oncology 2017 12, e107-e110DOI: (10.1016/j.jtho.2017.04.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Computed tomography scan of the left adrenal metastases before (A) and after (B) afatinib treatment showing stable disease in contrast to new liver metastases appearing at the time of disease progression, before (C) and after (D). Journal of Thoracic Oncology 2017 12, e107-e110DOI: (10.1016/j.jtho.2017.04.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 5 Graphic depiction of DNA splice site and protein fusion products solute carrier family 34 member 2 (SLC3A2)–neuregulin 1 (NRG1) (A) and CD74 molecule (CD74)-NRG1 (B) along with depiction of how they drive ErbB-mediated cellular proliferation through overactive autocrine and paracrine signaling through the EGF-like domain. CRD, cysteine rich domain; HER2, erb-b2 receptor tyrosine kinase 2; HER3/4 erb-b2 receptor tyrosine kinase 3/4; PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; MHC, major histocompatibility complex; TM, Trans-membrane domain. Journal of Thoracic Oncology 2017 12, e107-e110DOI: (10.1016/j.jtho.2017.04.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions