Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib

Our plain-English summary of Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib, by N. Agatsuma, Y. Yasuda, H. Ozasa (Journal of Thoracic Oncology, 2017).

The study

• Authors: N. Agatsuma, Y. Yasuda, H. Ozasa
• Journal: Journal of Thoracic Oncology
• Published: 2017;12(9):e141-e143
• Type of article: Case report, Letter
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter reported the case of a man with malignant pleural mesothelioma (MPM) carrying two uncommon EGFR mutations who was treated with afatinib. The patient was a 55-year-old Japanese man with cough, dyspnea and malignant pleural effusion. He had no significant medical history, no dust exposure, and a one-pack-year smoking history. Chest CT showed left-sided circumferential pleural thickening. FDG PET/CT showed high uptake in the left pleura, multiple lymph nodes, the left adrenal gland and the symphysis pubis. Earlier cytology of the pleural effusion had shown adenocarcinoma, so he was first diagnosed with advanced lung cancer and treated with carboplatin and pemetrexed. Immunohistochemistry on a cell block from the effusion was positive for podoplanin, calretinin and Wilms' tumor-1 and negative for TTF-1, Ber-EP4 and MOC31. PCR testing of EGFR exons 18 to 21 found G719C (exon 18) and S768I (exon 20) mutations. The diagnosis was revised to advanced epithelioid-type MPM with EGFR mutation. First-line and second-line cytotoxic therapies were not effective, and he was then given afatinib 40 mg daily. His pleural effusion was controlled, his lymph node and bone metastases shrank after 43 days, and a partial response by RECIST was achieved. Grade 2 diarrhea was controlled with loperamide. Progression-free survival on afatinib was 65 days, after which he was transferred for best supportive care. The authors stated this was the first reported MPM with both mutations and called for further study of afatinib in EGFR-mutated MPM.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This letter was a case report about one patient, a 55-year-old Japanese man with cough and shortness of breath and cancer-related fluid around the lung. The authors reported that he had no dust exposure. The letter does not mention asbestos. Cells in the fluid were first read as adenocarcinoma, and he was treated for advanced lung cancer with carboplatin and pemetrexed. Cell staining was positive for podoplanin, calretinin and Wilm's tumor-1, and a PCR-based genetic test found two uncommon EGFR mutations, G719C and S768I; the diagnosis was changed to advanced epithelioid-type malignant pleural mesothelioma. After first-line and second-line chemotherapy failed, he was given afatinib, 40 mg daily. His fluid was brought under control, his lymph node and bone metastases shrank after 43 days, and a partial response was recorded. He had grade 2 diarrhea, controlled with loperamide. His disease did not progress for 65 days on afatinib. His condition then worsened and he was moved to supportive care. The authors called this the first such case and said further study is needed to confirm afatinib's effectiveness in mesothelioma with EGFR mutations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report (letter to the editor) describing a single patient
• Who was studied: One 55-year-old Japanese man with cough and shortness of breath, transferred to the authors' hospital (Kyoto University) for treatment of malignant pleural effusion
• Exposure: No asbestos exposure was studied or mentioned. The patient was reported to have no dust exposure and a one pack-year smoking history. The treatment described was afatinib, 40 mg daily.
• Main results:
  • Earlier cytology of the pleural fluid showed adenocarcinoma, so the patient was first diagnosed with advanced lung cancer and treated with carboplatin and pemetrexed.
  • On immunohistochemical staining, tumor cells from the pleural fluid were positive for podoplanin, calretinin and Wilm's tumor-1, and negative for thyroid transcription factor 1, Ber-EP4 and MOC31.
  • A polymerase chain reaction (PCR-Invader) test of EGFR exons 18 to 21 found the mutations G719C (exon 18) and S768I (exon 20), and the diagnosis was changed to advanced epithelioid-type malignant pleural mesothelioma with EGFR mutation.
  • After first-line and second-line cytotoxic therapies were not effective, afatinib 40 mg daily controlled the pleural effusion, the lymph node and bone metastases shrank after 43 days, and a partial response by RECIST was achieved.
  • The patient had grade 2 diarrhea, which was well controlled by loperamide.
  • Progression-free survival on afatinib was 65 days. After progression the patient's condition worsened and he was transferred to another hospital for best supportive care.
• The authors' conclusion: The authors concluded that this was the first reported case of malignant pleural mesothelioma with both G719C and S768I EGFR mutations successfully treated with afatinib, and that further study is needed to confirm afatinib's efficacy in mesothelioma with EGFR mutations.
• Limitations the authors state:
  • The authors stated that further study is needed to confirm afatinib's efficacy for mesothelioma with EGFR mutations.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, EGFR, Dyspnea, Pleural Effusion, Pleural Thickening, Pleura, Cytology, Adenocarcinoma.

Related studies

• Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany — V. Schildgen, O. Pabst, et al. (2015)
• Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations — M.G. Zauderer, M. Bott, et al. (2013)
• Association between lung cancer somatic mutations and occupational exposure in never-smokers — C. Paris, P. Do, et al. (2017)
• Pulmonary adenocarcinoma with epidermal growth factor receptor-mutations in asbestos exposed non-smokers: A case series — R.L. Kradin, J. Iafrate, et al. (2017)
• Giant solitary fibrous tumor of the liver with metastasis to the skeletal system successfully treated with trisegmentectomy — S. Yilmaz, V. Kirimlioglu, et al. (2000)
• IgG4-related pleural disease with aortitis and submandibular glands involvement successfully treated with corticosteroid: case-based review — S. Okamoto, H. Tsuboi, et al. (2020)

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