How to Treat EGFR-Mutated Non–Small Cell Lung Cancer

•Mutations in the EGFR gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous EGFR mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation. Common side effects include acneiform rash, diarrhea, and paronychia. Osimertinib has also been associated with cardiomyopathy (∼1.4%-2.4%) and prolongation of the QT interval (2.7%).•In our experience, osimertinib-induced cardiomyopathy can be managed with the cessation of osimertinib and the initiation of guideline-directed therapy. Given that osimertinib is often the best available therapy, rechallenging with osimertinib often favors benefit over risk. Safe rechallenge with osimertinib is demonstrated in this case.