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Osimertinib is the standard of care for the first-line treatment of EGFR -mutated NSCLC. We report a case of a 52-year-old woman who developed life-threatening myopathy because of treatment with osimertinib. Limited instances of myositis have been previously reported in the literature; however, none have resulted in life-threatening oropharyngeal and respiratory muscle weakness as seen in this case. Care should be taken in administering osimertinib concurrently with other medications metabolized by the CYP3A4 system, and ongoing work to identify patients at risk for severe reactions is necessary. The use of routine creatinine phosphokinase monitoring should be considered as part of oncologic management., (© 2021 The Authors.)