A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib Helena A. Yu,

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A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib Helena A. Yu, MD, Leslie Perez, BS, Qing Chang, PhD, Sizhi P. Gao, PhD, Mark G. Kris, MD, Gregory J. Riely, MD, PhD, Jacqueline Bromberg, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 1, Pages 102-109 (January 2017) DOI: 10.1016/j.jtho.2016.08.140 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Best response of target lesions (Response Evaluation Criteria in Solid Tumors, version 1.1) in all patients with a radiographic assessment of response. Three patients without follow-up imaging were excluded. Pos., positive; Neg., negative. Journal of Thoracic Oncology 2017 12, 102-109DOI: (10.1016/j.jtho.2016.08.140) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Exosome EGFR levels in response to erlotinib and ruxolitinib. (A) H1975 (EGFR L858R-T790M) cancer cells were treated with vehicle (C) or ruxolitinib (1 mM) and erlotinib (125 nM) for 48 hours, and both cell lysates and lysates from exosomes isolated from the conditioned media of these cells were analyzed for EGFR, tubulin, and tsg101 (an exosomal protein) by Western blot analysis. (B) Exosomes were isolated from the plasma of patients before therapy (C1D1) and 2 weeks, 30 days, or 60 days after the commencement of ruxolitinib therapy. Exosomes from four healthy individuals (healthy controls) were isolated from plasma. Protein levels were measured and EGFR concentration (pg/mL) was determined for 2 mg of exosomal protein. Reductions in exosomal EGFR levels after the initiation of therapy are denoted in orange, no change is denoted in gray, and increases are denoted in blue. Time (months) receiving treatment (Rx) is indicated below each patient. Data are reported as the mean ± SD of three independent experiments. p Values refer to Student's t test. C, control; TKI, EGFR tyrosine kinase inhibitor; Ji, Janus Kinus inhibitor; *p < 0.05; **p < 0.005. Journal of Thoracic Oncology 2017 12, 102-109DOI: (10.1016/j.jtho.2016.08.140) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions