Osimertinib
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Acquired resistance: case report A woman in her late 50s [exact age not stated] acquired resistance during treatment with osimertinib for progressive lung adenocarcinoma. The woman, who had undergone surgery for lung adenocarcinoma at the age of 54 years, presented with recurrent lung tumour 16 months later. She received several lines of treatment comprising gefitinib, pemetrexed, erlotinib and then vinorelbine. Due to progressive lung metastasis, she underwent percutaneous CT guided re-biopsy and EGFR mutation assay showed H835L+L833V and T790M mutations. She then received osimertinib [route and dosage not stated] after afatinib failure, and had a response that lasted for 19 months. While on osimertinib treatment, she developed dyspnoea and a chest CT scan revealed progressive right lower lung collapse and pleural effusion. Bronchoscopy showed tumour eruption at the proximal right intermediate bronchus, causing lumen narrowing. Biopsy revealed lung tissue with squamous cell carcinma (SCC), composed of sheets and clusters of dysplastic squamous cells. The tumour cells were immunoreactive for p40 and non-reactive for thyroid transcription factor 1 (TTF-1). Programmed death ligand 1 staining of the tumour by 22C3 showed a 0% tumour proportion score. The woman received pembrolizumab and paclitaxel for 1 month with clinical deterioration. Mutation analysis of the squamous cell carcinoma performed by next generation sequencing showed complex genomic alteration including EGFR H835L+L833V and T790M mutations, TP53 mutation and mTOR amplification. After discussion with the patient, she received everolimus for 2 weeks, and osimertinib 80mg was added. A CT scan of the chest one month later showed regression of the endobronchial tumour and reexpansion of the lung. However, progression occurred in the liver and bone after 3 months of the treatment. Chiang C-L, et al. Squamous cell carcinoma transformation after acquired resistance to osimertinib in a patient with lung adenocarcinoma harboring uncommon EGFR 803500789 mutation. Journal of the Formosan Medical Association 119: 1439-1441, No. 9, Sep 2020. Available from: URL: http://doi.org/10.1016/j.jfma.2019.12.017
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Reactions 12 Sep 2020 No. 1821
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