Secondary Resistance to Erlotinib: Acquired T790M Mutation and Small-Cell Lung Cancer Transformation in the Same Patient Vincent Fallet, MD, Anne-Marie.

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Secondary Resistance to Erlotinib: Acquired T790M Mutation and Small-Cell Lung Cancer Transformation in the Same Patient Vincent Fallet, MD, Anne-Marie Ruppert, MD, Virginie Poulot, Roger Lacave, MD, PhD, Laure Belmont, MD, Martine Antoine, MD, Jacques Cadranel, MD, PhD, Marie Wislez, MD, PhD, Armelle Lavolé, MD Journal of Thoracic Oncology Volume 7, Issue 6, Pages 1061-1063 (June 2012) DOI: 10.1097/JTO.0b013e31824fea45 Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 CT scan evolution. A, June 2010: Alveolar opacity of the right upper lobe before erlotinib introduction. B, Major response after 2 months with erlotinib. C, June 2011: Mass of the right upper lobe corresponding to the SCLC transformation. D, Response of the right upper lobe mass with progression of the alveolar opacity, after one cycle of cisplatin and etoposide with erlotinib continuation. CT, computed tomography; SCLC, small-cell lung cancer. Journal of Thoracic Oncology 2012 7, 1061-1063DOI: (10.1097/JTO.0b013e31824fea45) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Resistance as small-cell lung cancer. A, Pathological analysis of bronchial biopsy specimen showing SCLC transformation. Small cells with round or oval nuclei and sparse cytoplasm. B, Sequencing chromatogram showing an exon 19 EGFR deletion (black bar) in DNA extract from SCLC biopsy specimen. SCLC, small cell lung cancer; EGFR, endothelial growth factor receptor. Journal of Thoracic Oncology 2012 7, 1061-1063DOI: (10.1097/JTO.0b013e31824fea45) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Resistance as T790M mutation. A, Cytological analysis of bronchial aspirate showing adenocarcinoma cells. Monolayered sheet of cells with uniform, round nuclei; fine nuclear chromatin; and intranuclear cytoplasmic inclusion bodies. B, Sequencing chromatograms of exon 20 for EGFR demonstrate the T790M mutation (c.2369C > T; p.Thr790Met) at exon 20) in DNA extract from adenocarcinoma cells from bronchial aspirate specimen. A red arrow indicates the mutation at nucleotide 2369 (C > K [C + T]), which leads to substitution of Threonine (ACG) for Methionine (ATG) at position 790. EGFR, endothelial growth factor receptor. Journal of Thoracic Oncology 2012 7, 1061-1063DOI: (10.1097/JTO.0b013e31824fea45) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions