FDA Approves Crizotinib for ALK-Positive Inflammatory Myofibroblastic Tumors

The FDA has approved crizotinib (Xalkori) for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory ALK-positive myofibroblastic tumors (IMT).¹

The safety and efficacy of crizotinib were evaluated in the multicenter, single-arm, open-label trials ADVL0912 (NCT00939770), which enrolled 14 pediatric patients, and A8081013 (NCT01121588), which enrolled 7 adult patients. All of the enrolled patients had unresectable, recurrent, or refractory ALK-positive IMT.

Both trials’ major efficacy outcome measure was objective response rate (ORR). Twelve of the 14 pediatric patients (86%, 95% CI: 57, 98) enrolled in ADVL0912 had an objective response as assessed by an independent review committee, whereas 5 of the 7 adult patients had objective responses.

The most common adverse events (AEs) among pediatric patients (≥35%) administered crizotinib were vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. The most frequent AEs (≥35%) among the adult patients were vision disorders, nausea, and edema.

Crizotinib is a multitargeted small molecule tyrosine kinase inhibitor that was originally developed as an inhibitor of the mesenchymal epithelial transition growth factor (c-MET). The drug is also a potent inhibitor of ALK phosphorylation and signal transduction.²

Crizotinib has shown concentration-dependent inhibition of ALK and c-Met phosphorylation in cell-based assays using tumor cell lines. It has also shown antitumor activity in mice bearing tumor xenografts that express EML4- or NPM-ALK fusion proteins or c-Met.

Crizotinib has been approved to treat non-small cell lung cancer that has spread to other parts of the body and is caused by a defect in either the ALK or ROS1 gene.

References

1. FDA approves crizotinib for ALK-positive inflammatory myofibroblastic tumor. FDA. News release. July 15, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizotinib-alk-positive-inflammatory-myofibroblastic-tumor?utm_medium=email&utm_source=govdelivery

2. Sahu A, Prabhash K, Noronha V, Joshi A, Desai S. Crizotinib: A comprehensive review. South Asian J Cancer. 2013 Apr;2(2):91-7. doi: 10.4103/2278-330X.110506. PMID: 24455567; PMCID: PMC3876666.