Axitinib

Axitinib (AG013736; trade name Inlyta) is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types.RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK).c-MET inhibitor: Cabozantinib (also VEGFR2). Axitinib (AG013736; trade name Inlyta) is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types. It was approved for RCC by the U.S. Food and Drug Administration after showing a modest increase in progression-free survival, though there have been reports of fatal adverse effects. It has received approval for use as a treatment for renal cell carcinoma from US FDA (27 January 2012), EMA (13 September 2012), UK MHRA (3 September 2012) and Australian TGA (26 July 2012) . A Phase II clinical trial showed good response in combination chemotherapy with gemcitabine for advanced pancreatic cancer. However, Pfizer reported on January 30, 2009 that Phase III clinical trials of the drug when used in combination with gemcitabine showed no evidence of improved survival rates over treatments using gemcitabine alone for advanced pancreatic cancer and halted the trial. In 2010, a Phase III trial for previously treated metastatic renal cell carcinoma (mRCC) showed significantly extended progression-free survival when compared to sorafenib. In December 2011, the Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend that US FDA approve axitinib for the second-line treatment of patients with advanced renal cell carcinoma (RCC), based on the results of the Phase III trial comparing axitinib and sorafenib. It has also been studied in combination with the ALK1 inhibitor dalantercept. A study published in 2015 showed that axitinib effectively inhibits a mutated gene (BCR-ABL1) that is common in chronic myeloid leukemias and adult acute lymphoblastic leukemias which have become resistant to other tyrosine kinase inhibitors like imatinib. This is one of the first examples of a new indication for an existing drug being discovered by screening known drugs using a patient's own cells. The only contraindication to axitinib is hypersensitivity to axitinib. Cautions include: