Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial Kenneth S. Thress, PhD, Vivien.

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Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial Kenneth S. Thress, PhD, Vivien Jacobs, BSc, Helen K. Angell, PhD, James Chih-Hsin Yang, MD, PhD, Lecia V. Sequist, MD, MPH, Fiona Blackhall, MD, PhD, Wu-Chou Su, MD, Martin Schuler, MD, Jürgen Wolf, MD, Kathryn A. Gold, MD, Mireille Cantarini, MD, J. Carl Barrett, PhD, Pasi A. Jänne, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 10, Pages 1588-1594 (October 2017) DOI: 10.1016/j.jtho.2017.07.011 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Flow diagram of the eligible study population. Of the 125 patients who provided signed informed consent to participate in the paired biopsy sample analyses, 67 had T790M-positive tumors by central testing. Predose tumor biopsy samples were successfully collected from 61 patients, and both predose and postdose biopsy samples were collected from 42 patients. Of these, 24 patients had viable predose and postdose samples and were eligible for biomarker analyses. Journal of Thoracic Oncology 2017 12, 1588-1594DOI: (10.1016/j.jtho.2017.07.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Kaplan-Meier curves of progression-free survival (PFS) (A) in patients from whom both a predose and postdose biopsy sample were successfully collected and those from whom a predose biopsy sample but no viable postdose tumor biopsy sample was collected. Waterfall plots showing best percentage change in target lesion diameter for evaluable patients from whom both predose and postdose biopsy samples were successfully collected (B) and those from whom a predose biopsy sample but no viable postdose tumor biopsy sample was collected (C). Abbreviations: CI, confidence interval; NC, not calculable; PD, progressive disease; PR, partial response. Journal of Thoracic Oncology 2017 12, 1588-1594DOI: (10.1016/j.jtho.2017.07.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Line plots showing the predose and postdose H-score for matched samples for each individual patient stained for membrane phospho-EGFR (pEGFR) (A), phospho-S6 (S6) (B) and phospho-AKT (pAKT) (C). For tumor cells positive for membrane programmed death ligand 1 (PD-L1) (D), the percentage of positive tumor cells is shown. For CD8 (E) and immune cells positive for PD-L1 (F), cells per mm2 and percentage of immune cells positive are shown, respectively. Change (decrease, increase, or no change) is indicated, as is the dose of osimertinib received (80 or 160 mg). Abbreviation: CD8, cytotoxic T-cell. Journal of Thoracic Oncology 2017 12, 1588-1594DOI: (10.1016/j.jtho.2017.07.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions