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      Different incidence of interstitial lung disease according to different kinds of EGFR‐tyrosine kinase inhibitors administered immediately before and/or after anti‐PD‐1 antibodies in lung cancer

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          Abstract

          Background

          The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR‐tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD‐1 antibody.

          Methods

          We analyzed the data of 26 patients who underwent treatment with EGFR‐TKIs immediately before and/or after the administration of an anti‐PD‐1 antibody.

          Results

          Four out of the 26 patients developed ILD during EGFR‐TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti‐PD‐1 antibody. Three of 12 patients who underwent EGFR‐TKI therapy immediately after anti‐PD‐1 antibody treatment experienced osimertinib‐induced ILD. ILD was not observed in the five patients administered an anti‐PD‐1 antibody followed by first or second‐generation EGFR‐TKIs.

          Conclusion

          ILD was observed in the treatment sequence of an anti‐PD‐1 antibody followed by osimertinib, but not with first or second‐generation EGFR‐TKIs.

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          Most cited references6

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          136O: Osimertinib combined with durvalumab in EGFR-mutant non-small cell lung cancer: Results from the TATTON phase Ib trial.

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            Nivolumab-induced interstitial lung disease analysis of two phase II studies patients with recurrent or advanced non-small-cell lung cancer.

            Drug-induced interstitial lung disease (ILD) is often associated with high mortality; however it is difficult to predict and manage. we examined the clinical findings and imaging characteristics of nivolumab induced ILD reported in the two phase II studies patients with recurrent or advanced non-small-cell lung cancer.
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              Osimertinib in Japanese patients with EGFR T790M mutation‐positive advanced non‐small‐cell lung cancer: AURA 3 trial

              Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first‐line treatment for patients with EGFR mutant non‐small‐cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third‐generation EGFR‐TKI that can inhibit the kinase even when the common resistance‐conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first‐line EGFR‐TKI treatment. AURA3 was a randomized (2:1), open‐label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum‐based therapy plus pemetrexed (500 mg/m2) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first‐line EGFR‐TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end‐point was progression‐free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum‐pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13‐0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum‐pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum‐pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation‐positive NSCLC whose disease has progressed following first‐line EGFR‐TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.)
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                Author and article information

                Contributors
                kkaira1970@yahoo.co.jp
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                12 March 2019
                April 2019
                : 10
                : 4 ( doiID: 10.1111/tca.2019.10.issue-4 )
                : 975-979
                Affiliations
                [ 1 ] Department of Respiratory Medicine Comprehensive Cancer Center, International Medical Center Saitama Medical University Saitama Japan
                Author notes
                [*] [* ] Correspondence

                Kyoichi Kaira, Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397‐1 Yamane, Hidaka‐City, Saitama 350‐1298, Japan.

                Tel: +81 42 984 4111

                Fax: +81 42 984 4741

                Email: kkaira1970@ 123456yahoo.co.jp

                Author information
                https://orcid.org/0000-0001-5548-7686
                Article
                TCA13039
                10.1111/1759-7714.13039
                6449223
                30864291
                18a989e1-1eb4-4b63-9d03-380d9946e5d6
                © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 28 January 2019
                : 18 February 2019
                : 19 February 2019
                Page count
                Figures: 1, Tables: 2, Pages: 5, Words: 2431
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                tca13039
                April 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:04.04.2019

                ild,afatinib,egfr‐tki,nivolumab,osimertinib
                ild, afatinib, egfr‐tki, nivolumab, osimertinib

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