Osimertinib

Osimertinib (previously known as mereletinib; trade name Tagrisso) is a medication used to treat non-small-cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Developed by AstraZeneca, the medication was approved as a cancer treatment in 2017 by both the Food and Drug Administration and the European Commission.RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK).c-MET inhibitor: Cabozantinib (also VEGFR2). Osimertinib (previously known as mereletinib; trade name Tagrisso) is a medication used to treat non-small-cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Developed by AstraZeneca, the medication was approved as a cancer treatment in 2017 by both the Food and Drug Administration and the European Commission. Osimertinib is used to treat locally advanced or metastatic non-small-cell lung cancer (NSCLC), if the cancer cells are positive for the T790M mutation in the gene coding for EGFR. The T790M mutation may be de novo or acquired following first-line treatment with other tyrosine kinase inhibitors (TKIs), such as gefitinib and afatinib. In the USA, T790M status of the patient prior to treatment with osimertinib must be detected by a federally approved companion diagnostic test. The Food and Drug Administration (FDA) has approved FoundationOne CDx for this purpose. In Europe and elsewhere, T790M mutations may be determined by a validated and suitably sensitive next-generation sequencing assay. In people treated with osimertinib, resistance usually develops within approximately 10 months. Resistance mediated by an exon 20 C797S mutation accounts for the majority of resistance cases. It causes fetal harm, so should not be used in women who are pregnant, and women who take it should avoid becoming pregnant. Caution should be taken in people with a history of interstitial lung disease (ILD) were excluded from clinical trials, as the drug can cause severe ILD or pneumonia. Caution should also be taken in people with a predisposition to long QT syndrome as the drug can provoke this. Very common (greater than 10% of clinical trial subjects) adverse effects include diarrhea, stomatitis, rashes, dry or itchy skin, infections where finger or toenails abut skin, low platelet counts, low leukocyte counts, and low neutrophil counts. Common (between 1% and 10% of clinical trial subjects) adverse effects include interstitial lung disease. Osimertinib is metabolized by CYP3A4 and CYP3A5, so substances that strongly inhibit either enyzme, like macrolide antibiotics, antifungals, and antivirals may increase exposure to osimertinib, and substances like rifampicin that activate either enzyme will decrease the effectiveness of osimertinib.