March 14, 2015 – The American Food and Drug Administration (FDA) just approved Crizotinib (Xalkori) to treat the patient subpopulation with advanced (metastatic) non-small cell lung cancer (NSCLC) whose tumors have an ROS-1 gene alteration. Crizotinib (Xalkori) is the first and only FDA approved treatment for patients with ROS-1 positive NSCLC.
ROS-1 is a porto-oncogene that codes for the proto-oncogene tyrosine-kinase protein ROS-1, is highly expressed in a variety of tumor cell lines, and belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The ROS-1 protein is a type I integral membrane protein, and may function as a growth or differentiation factor receptor.
Gene rearrangements involving the ROS-1 gene were first detected in glioblastoma tumors and cell lines. ROS-1 gene alterations, thought to lead to abnormal cells, have been identified in various cancers, including NSCLC. ROS-1 gene alterations are present in approximately 1 percent of patients with NSCLC. Crizotinib (Xalkori) blocks the activity of the ROS-1 protein in tumors that have ROS-1 gene alterations, and this effect on ROS-1 may prevent NSCLC from growing and spreading. The overall patient and disease characteristics of NSCLC with ROS-1 gene alterations appear similar to NSCLC with anaplastic lymphoma kinase (ALK) gene alterations, for which Crizotinib (Xalkori) use was previously approved to treat certain patients with late-stage NSCLC that expresses an abnormal ALK gene.
The efficacy of Crizotinib (Xalkori) for the treatment of patients with ROS-1 positive tumors was evaluated in a multi-center, single-arm study of 50 patients with ROS-1 positive metastatic NSCLC. Patients received Crizotinib (Xalkori) twice daily to measure the drug’s effect on their lung cancer tumors. The studies were designed to measure overall response rate, the percentage of patients who experienced complete or partial shrinkage of their tumors. Results showed 66 percent of participants experienced a complete or partial shrinkage of their NSCLC tumors, an effect that lasted a median of 18.3 months.
The safety results of this study were generally consistent with the safety profile of Crizotinib (Xalkori) evaluated in 1,669 patients with ALK-positive metastatic NSCLC. The most common side effects of Crizotinib (Xalkori) are vision disorders, nausea, diarrhea, vomiting, swelling (edema), constipation, liver problems (elevated transaminases), fatigue, decreased appetite, upper respiratory infection, and dizziness and numbness or tingling in the hands or feet (neuropathy). Crizotinib (Xalkori) may cause serious side effects, including liver problems, life-threatening or fatal inflammation of the lungs, abnormal heartbeats and partial or complete loss of vision in one or both eyes. We may also note here, that very recently Swissmedic, the Swiss Institute for Therapeutic Products, has alerted patients and physicians alike about the occurrence of sometimes fatal heart insufficiency in patients treated with Crizotinib (Xalkori) as reported in Thasso Post.