Osimertinib

Abstract

Acquired drug resistance: 3 case reports In a study involving 67 patients with advanced non-small cell lung cancer (NSCLC) from December 2018 to October 2019, three patients including a man and two women aged 53–62 years old were described, who developed acquired drug resistance while receiving treatment with osimertinib for advanced NSCLC [dosages not stated]. Patient 1: A 53-year-old woman, who had advanced NSCLC (left lung adenocarcinoma stage IVB), had been receiving treatment with oral osimertinib. Subsequently, exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975 were extracted and sequenced, while blood sample was collected from her and the results were compared with plasma exosome sequencing before and after the appearance of drug resistance. Exosome derived miRNAs had significantly increased expression levels and were screened. The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of sample indicated osimertinib resistance. Patient 2: A 62-year-old man, who had advanced NSCLC (left lung adenocarcinoma) was initially treated with gefitinib. One year later, he started receiving treatment with oral osimertinib due to new brain and bone metastasis. The cancer progressed after 19 months. Subsequently, exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975 were extracted and sequenced, while blood sample was collected from him and the results were compared with plasma exosome sequencing before and after the appearance of drug resistance. Exosome derived miRNAs had significantly increased expression levels and were screened. The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of sample indicated osimertinib resistance. Patient 3: A 58-year-old woman, who had advanced NSCLC (left lung adenocarcinoma stage IVB), had been receiving treatment with oral osimertinib. Subsequently, exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975 were extracted and sequenced, while blood sample was collected from her and the results were compared with plasma exosome sequencing before and after the appearance of drug resistance. Exosome derived miRNAs had significantly increased expression levels and were screened. The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of sample indicated osimertinib resistance.