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Journal Article
Review
Osimertinib for the treatment of patients with EGFR mutation-positive non-small cell lung cancer.
Drugs of Today 2018 June
Epidermal growth factor receptor (EGFR) mutations, mostly seen in exon 19 or exon 21, are present in roughly 50% of patients with advanced non-small cell lung cancer (NSCLC) of Asian ethnicity compared with 12% in Caucasians. EGFR-mutated NSCLC patients have an increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib or afatinib, showing superior response, progression-free survival and overall survival rates with EGFR-TKIs than with platinum doublet chemotherapy, which makes EGFR-TKIs the standard of care in this subgroup of NSCLC patients. This has been the most important step toward molecular-guided precision therapy for NSCLC. Despite the initial rapid and durable clinical responses, acquired resistance to EGFR-TKIs has been found to eventually develop in most cases, with disease progression observed mostly within 9-12 months after treatment. One of the most important mechanisms for resistance to EGFR-TKI therapy is the substitution of threonine to methionine (T790M) on exon 20 of the EGFR gene, which occurs in 49% to 60% of patients. Osimertinib mesylate (formerly AZD-9291) is a potent third-generation TKI which irreversibly inhibits mutated EGFR alleles, including T790M. This review summarizes osimertinib's pharmacology, pharmacokinetics, safety, side effects and clinical utility in the treatment of EGFR-mutated advanced NSCLC.
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