The Toxicity of Osimertinib in Cancer Therapy

Abstract

Osimertinib is a novel 3rd-generation TKI which targets the EGFR in NSCLC. It inhibits the phosphorylation of EGFR, thereby inhibits proliferation of NSCLC. Thus, Osimertinib is widely used in the treatment of lung cancer, as well as other types of cancers such as glioblastoma (GBM). However, there are still some drawbacks. Osimertinib can suppress stromal cells in the bone marrow, thereby leading to the aplastic anaemia. Osimertinib can also contribute to dermatposis. Some patients are diagnosed with kidney and heart failure after the treatment, which is suspected the failures associated with the Osimertinib. Even though the drug resistance of Osimertinib is relatively low, the drug resistance cannot be completely ignored. The mechanisms of drug resistance include EGFR-dependent mechanism with the loss of T790M mutation, as well as non-EGFR-dependent mechanism due to the amplification of allele wt-EGFR and existence of allele EGFR-ex19del. In addition, the price of Osimertinib is still high in most regions. Future studies may focus on how to reduce the toxicity to organs and the drug resistance, thereby providing a direction for the fourth-generation TKI.