The FDA has approved crizotinib as a therapeutic option for patients with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumors.
The FDA has approved crizotinib (Xalkori) for patients with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumors (IMT), according to a news release shared by the agency. 1
Two multicenter, single-arm, open-label trials supported the regulatory decision: the ADVL0912 trial (NCT00939770), which enrolled 14 pediatric patients, and the A8081013 trial (NCT01121588), which enrolled 7 adult patients.
Objective responses were observed in 5 out of the 7 adult patients, and 12 out of the 14 pediatric patients—achieving an objective response rate (ORR) of 86%, (95%, 57%-98%) meeting that trial’s major efficacy outcome. Responses were assessed by an independent review committee.
Among pediatric patients who received crizotinib, the most common adverse events (AEs), occurring in at least 35% of patients, included vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. In the adult population, vision disorders, nausea, and edema were the most common AEs.
The advised amount of crizotinib in adult patients is 250 mg orally twice daily until disease progression or unacceptable toxicity. For pediatric patients, the recommended dose is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity.
Crizotinib is a kinase inhibitor which is also approved for patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors are ALK- or ROS1-positive as detected by an FDA-approved test and for pediatric patients who are 1 year and older and young adults with relapsed or refractory, systematic anaplastic large cell lymphoma that is ALK-positive.
Crizotinib comes with a warning for hepatotoxicity: fatal hepatotoxicity has occurred with the drug and patients undergoing this treatment should receive monitoring via periodic liver testing.2 If hepatotoxicity occurs, the agent may be temporarily suspense, reduced, or discontinues. Interstitial lung disease and pneumonitis may also occur with usage. If this occurs, the agent should be permanently discontinued.
Other rare but potentially severe complications associated with use include QT interval prolongation, bradycardia, severe visual loss, gastrointestinal toxicity, and embryo-fetal toxicity. Regular monitoring and early intervention in the case of occurrence is advised.