Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A Meta- analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in.

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Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A Meta- analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in Advanced EGFR-Mutated Non–Small Cell Lung Cancer Pei Ni Ding, MBBChir, Sarah J. Lord, MSc, Val Gebski, MStat, Matthew Links, PhD, Victoria Bray, PhD, Richard J. Gralla, MD, James Chih-Hsin Yang, PhD, Chee Khoon Lee, PhD Journal of Thoracic Oncology Volume 12, Issue 4, Pages 633-643 (April 2017) DOI: 10.1016/j.jtho.2016.11.2236 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Flow diagram showing inclusion and exclusion of studies. TKI, tyrosine kinase inhibitor. Journal of Thoracic Oncology 2017 12, 633-643DOI: (10.1016/j.jtho.2016.11.2236) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Forest plot showing pooled risk ratio for (i) toxic death, (ii) grade 3 and 4 adverse events, and (iii) discontinuation of treatment because of adverse events with (A) afatinib versus with gefitinib, (B) afatinib versus with erlotinib, and (C) gefitinib versus with erlotinib. The risk ratio for each adverse event is represented by the square, and the horizontal line crossing the square represents the 95% confidence interval (CI). Journal of Thoracic Oncology 2017 12, 633-643DOI: (10.1016/j.jtho.2016.11.2236) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Forest plot showing the pooled risk ratio for specific EGFR tyrosine kinase inhibitor treatment–related grade 3 and 4 adverse events with (A) afatinib versus gefitinib, (B) afatinib versus erlotinib, and (C) gefitinib versus erlotinib. The risk ratio for each adverse event is represented by a square, and the horizontal lines crossing the squares represent the 95% confidence interval (CI). Journal of Thoracic Oncology 2017 12, 633-643DOI: (10.1016/j.jtho.2016.11.2236) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Confidence associated with absolute 18-month progression-free survival (PFS) benefit of afatinib compared with gefitinib in the LUX-Lung 7 trial4 and absolute overall treatment-related grade 3 and 4 adverse events. Dashed line is the physician’s estimate of the additional anticipated benefit and maximum additional adverse event rates acceptable for a 40-year-old patient assessed as having a performance status of 0. Dotted line is the physician’s estimate of additional anticipated benefit and maximum additional adverse event rates acceptable for an 80-year-old patient assessed as having a performance status of 2. Journal of Thoracic Oncology 2017 12, 633-643DOI: (10.1016/j.jtho.2016.11.2236) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions