Crizotinib Receives FDA Approval for ALK-Positive Inflammatory Myofibroblastic Tumor

For unresectable, recurrent or treatment-resistant ALK-positive inflammatory myofibroblastic tumors, crizotinib (Xalkori, Pfizer Inc.) received FDA (US Food and Drug Administration) approval on July 14, 2022, for pediatric and adult patients aged 1 year and older.

What Is an Inflammatory Myofibroblastic Tumor?

An inflammatory myofibroblastic tumor (IMT) forms on mucosal surfaces and in tissues called the mesentery. Mucosal surfaces are found in your eyes, nose, mouth, digestive system, lungs, and genital and urinary tracts. The mesentery connects the organs in your abdomen. IMT usually begins in the lungs but may start in the bladder, uterus, larynx, stomach, liver or intestine. IMT may also be called inflammatory fibrosarcoma or IMFT. Among the rare tumors is this one.

Inflammatory myofibroblastic tumor (IMT) is named for the two types of cells found in the tumor. IMT consists of a type of cell called a myofibroblast. Myofibroblasts help maintain the shape of organs and heal wounds. IMTs also contain many immune cells, making the tumor look "inflamed" like an infection; this is where the term inflammatory comes from.

IMT is usually benign, meaning it is not cancerous, and these tumor cells generally do not travel to other parts of the body. However, IMT may invade nearby tissue and cause many problems. IMT may grow in the way of important organs such as the lungs or stomach. In very rare cases, IMT metastasis may occur, meaning spread to distant organs.

IMTs are mostly found in children and young adults but may occur at any age.

We know that in some IMT cases, chromosomes (the parts of your cells containing all your genes) break apart and reassemble incorrectly. We call these types of mutations (genetic changes) fusions. These genetic changes may cause cells not to function as they should. In IMT, the ALK gene may fuse with other genes. Genetic tests identify this situation, and finding an ALK fusion in a tumor both supports its diagnosis as IMT and is an important determinant for treatment.

• Related topic: What Is an ALK Fusion?

FDA Approval Based on Two Clinical Trials

The safety and efficacy of crizotinib in ALK-positive inflammatory myofibroblastic tumors (IMT) were evaluated in two multicenter, single-arm, open-label studies involving 14 pediatric patients from the ADVL0912 study and 7 adult patients from the A8081013 study.

The main efficacy outcome measure in these clinical trials was the objective response rate. Among 14 pediatric patients, a total of 12 of the 14 patients (86%) experienced an objective response. Five of the seven adult patients had objective responses to treatment.

The most common (≥ 35%) side effects in pediatric patients were vomiting, nausea, diarrhea, abdominal pain, rash, visual impairment, upper respiratory tract infection, cough, fever, musculoskeletal pain, fatigue, edema, constipation and headache. The most common (≥ 35%) side effects in adults were visual disturbances, nausea and edema.

The recommended crizotinib dose in adults is 250 mg orally twice daily until disease progression or unacceptable side effects. The recommended pediatric dose is 280 mg/m2 orally twice daily until disease progression or unacceptable side effects.