Ceritinib

Ceritinib is a selective small-molecule inhibitor of anaplastic lymphoma kinase (ALK) and a second-generation ALK tyrosine kinase inhibitor. It was developed for the treatment of ALK-positive non-small cell lung cancer (NSCLC) and is marketed as Zykadia. Ceritinib is approved for adult patients whose disease has progressed on or who cannot tolerate crizotinib. It may also be studied in other ALK-driven cancers, including some ROS1-rearranged tumors, but its approved use centers on ALK-positive NSCLC.

Mechanism of action and pharmacology: Ceritinib binds to the ATP-binding site of ALK, inhibiting phosphorylation and downstream signaling necessary for tumor cell growth and survival. By targeting ALK-dependent pathways, it can produce tumor responses in crizotinib-resistant disease. The drug is metabolized primarily by the cytochrome P450 3A (CYP3A) system, and its exposure can be altered by strong CYP3A inhibitors or inducers.

Administration and dosing: The recommended dose is 750 mg taken orally once daily after an overnight fast. Food increases ceritinib exposure, so it is advised to take the dose on an empty stomach. Dose adjustments may be necessary for tolerability or drug interactions.

Safety and monitoring: Common adverse effects include diarrhea, nausea, vomiting, fatigue, decreased appetite, weight loss, and elevated liver enzymes. Serious risks include hepatotoxicity, interstitial lung disease or pneumonitis, and QT interval prolongation. Monitoring typically includes liver function tests, electrolytes, and cardiac monitoring as indicated.

See also: ALK inhibitors; crizotinib resistance; non-small cell lung cancer treatment.