II. Indications
- Lung Adenocarcinoma (ROS1+, metastatic)
III. Mechanism
- ROS1 Tyrosine-Protein Kinase
- Proto-oncogene ROS is encoded by the ROS1 gene
- ROS is a Protein associated with cell growth, via Tyrosine phosphorylation and receptor-mediated signaling
- Member of the sevenless subfamily of Tyrosine KinaseInsulin receptor genes
- ROS1 Inhibitors are small molecule, Tyrosine Kinase Inhibitors specific to ROS1 receptors
- Agents that block ROS1, suppress specific tumor cell growth
IV. Medications
-
Crizotinib (Xalkori)
- Also targets ALK (See ALK Inhibitor)
- Also blocks c-Met/hepatocyte growth factor receptor (HGFR)
- Adverse Effects include ILD, hepatotoxicity, Bradycardia, QT Prolongation
-
Entrectinib (Rozlytrek)
- Also targets NTRK (See NTRK Inhibitor)
- Risk of Neurotoxicity, Hepatotoxicity, skeletal Fractures, cardiotoxicity, Prolonged QTc, Hyperuricemia, ocular toxicity
- Avoid with strong CYP3A4 Inhibitors and inducers
V. Dosing
- See other references for disease specific dosing protocols
VI. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception
VII. Adverse Effects (based on Entrectinib)
- Cardiotoxicity
- Cognitive Impairment
- Fractures
- Hepatotoxicity
- Ocular Toxicity