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      Life‐threatening pneumonitis after first‐line treatment with osimertinib for primary T790M mutated non‐small cell lung cancer

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          Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR‐mutated non‐small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life‐threatening side effects have been reported. TKI‐induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR‐TKI pretreated patients. Here, we report a case of successful stabilization of a life‐threatening ILD in a de novo T790M mutated NSCLC during first‐line treatment with osimertinib. As osimertinib will be used more often in many EGFR‐positive NSCLC patients in the future, this potentially life‐threatening side effect should receive special attention, especially in first‐line treatment.

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          Most cited references 13

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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.

          Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced EGFR-mutated NSCLC. Estimating differences in toxicity between these EGFR TKIs is important for personalizing treatment.
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            Osimertinib-induced interstitial lung disease after treatment with anti-PD1 antibody

            Summary We report a case of a 38-year-old woman who was diagnosed with stage IV lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790 M mutation on exon 20. The patient was treated with osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) following treatment with nivolumab, an anti-Programmed Cell Death 1 (anti-PD1) antibody. After initiating osimertinib treatment, the patient began to complain of low-grade fever and shortness of breath without hypoxemia, and her chest radiograph and a CT scan revealed a remarkable antitumor response, although faint infiltrations were observed in the bilateral lung field. Bronchoalveolar lavage fluid mainly contained lymphocytes (CD4+/CD8+ ratio of 0.3), and a transbronchial lung biopsy specimen showed lymphocytic alveolitis with partial organization in several alveolar spaces. Therefore we diagnosed the patient with osimertinib-induced interstitial lung disease (ILD) after treatment with anti-PD1 antibody. We considered anti-PD1 therapies may be the risk factor of EGFR-TKI-induced ILD.
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              Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report.

              Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment.

                Author and article information

                Thorac Cancer
                Thorac Cancer
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                06 May 2020
                July 2020
                : 11
                : 7 ( doiID: 10.1111/tca.v11.7 )
                : 2044-2047
                [ 1 ] Department of Internal Medicine VIII, Medical Oncology and Pneumology Eberhard Karls University Tübingen Germany
                [ 2 ] Department of Internal Medicine II, Oncology, Hematology, Clinical Immunology and Rheumatology Eberhard Karls University Tübingen Germany
                [ 3 ] Department of Radiology University Hospital and Comprehensive Cancer Center Tübingen, Eberhard Karls University Tübingen Germany
                [ 4 ] Department of Internal Medicine, Medical Intensive Care Unit Eberhard Karls University Tübingen Germany
                [ 5 ] NPARU, University of Worcester Worcester UK
                Author notes
                [* ] Correspondence

                Maik Häntschel, Universitätsklinikum Tübingen, Medizinische Klinik VIII, Otfried‐Müller‐Str. 10, 72076 Tübingen, Germany.

                Tel: +49 7071 29‐82711

                Fax: +49 7071 29‐4475

                Email: maik.haentschel@

                © 2020 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 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 1, Tables: 0, Pages: 4, Words: 1764
                Case Report
                Case Reports
                Custom metadata
                July, 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:01.07.2020


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