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• W2748383514 abstract "Afatinib is effective for lung cancer harboring minor mutations of EGFR.1Yang J.C. Sequist L.V. Geater S.L. et al.Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.Lancet Oncol. 2015; 16: 830-838Abstract Full Text Full Text PDF PubMed Scopus (648) Google Scholar Here we report the first case in which malignant pleural mesothelioma (MPM) harboring minor mutations of EGFR was successfully treated with afatinib. Malignant pleural effusion was diagnosed in a 55-year-old Japanese man presenting with cough and dyspnea; he was transferred to our hospital for treatment. He had no significant medical history, no dust exposure, and a one–pack-year smoking history just before admission. Computed tomography of the chest revealed left-sided circumferential pleural thickening, and fludeoxyglucose F 18 positron emission tomography/computed tomography showed high tracer uptake in the left pleura, multiple lymph nodes, the left adrenal gland, and the symphysis pubis. As the previous cytologic examination of the patient's pleural effusion demonstrated adenocarcinoma, we initially diagnosed advanced lung cancer with pleural carcinomatosis and treated it with carboplatin and pemetrexed. For analysis of gene mutations, a cell block was made from pleural effusion. On immunohistochemical analysis, the tumor cells were positive for podoplanin, calretinin, and Wilm’s tumor-1 and negative for thyroid transcription factor 1, Ber-EP4, and MOC31 (Fig. 1). EGFR mutations were analyzed on selected regions of exons 18 to 21 by using the polymerase chain reaction with PCR-Invader (BML Inc., Tokyo, Japan), which revealed that the tumors harbored G719C in exon 18 and S768I in exon 20 mutations. Therefore, we rediagnosed the patient's disease as advanced epithelioid-type MPM with EGFR mutation. Because first-line and second-line cytotoxic therapies were not effective, the patient was treated with 40 mg of afatinib daily. His pleural effusion was brought under control, and his lymph node and bone metastasis shrank after 43 days, after which partial response based on the Response Evaluation Criteria in Solid Tumors was achieved (Fig. 2). He had grade 2 diarrhea, which was well controlled by loperamide. Finally, his progression-free survival during afatinib treatment lasted 65 days. After disease progression, his condition deteriorated and he was transferred to another hospital for best supportive care. EGFR mutations are rarely found in MPM. There are only two reports concerning EGFR mutations in MPM. EGFR mutations (T725M in exon 18, Q787Q in exon 20, and N816K in exon 20) were reported in three Japanese patients with MPM, and G719C mutations were reported in two German patients with MPM.2Enomoto Y. Kasai T. Takeda M. et al.Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma.J Clin Pathol. 2012; 65: 522-527Crossref PubMed Scopus (21) Google Scholar, 3Schildgen V. Pabst O. Tillmann R.L. et al.Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany.Appl Immunohistochem Mol Morphol. 2015; 23: 118-125Crossref PubMed Scopus (10) Google Scholar To our knowledge, this is the first case report of two EGFR mutations (G719C in exon 18 and S768I in exon 20) found in MPM. EGFR mutations are sometimes found in NSCLC. G719C and S768I mutations are rare even in NSCLC. G719X, L861G, and S768I are well known as uncommon mutations of EGFR. Although EGFR was highly expressed, erlotinib was not effective for MPM.4Garland L.L. Rankin C. Gandara D.R. et al.Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group study.J Clin Oncol. 2007; 25: 2406-2413Crossref PubMed Scopus (191) Google Scholar This may have been due to the poor sensitivity of uncommon mutations to erlotinib.5Banno E. Togashi Y. Nakamura Y. et al.Sensitivities to various epidermal growth factor receptor-tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: what is the optimal epidermal growth factor receptor-tyrosine kinase inhibitor?.Cancer Sci. 2016; 107: 1134-1140Crossref PubMed Scopus (71) Google Scholar In our case, afatinib was more effective than cytotoxic chemotherapy. Here we have reported the first case of MPM harboring both G719C and S768I mutations of EGFR, which was successfully treated with afatinib. Further study is necessary for confirming the efficacy of afatinib for MPM with EGFR mutations." @default.
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• W2748383514 date "2017-09-01" @default.
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• W2748383514 title "Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib" @default.
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• W2748383514 doi "https://doi.org/10.1016/j.jtho.2017.04.028" @default.
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