Crizotinib Approved for Treatment of ALK-Positive Inflammatory Myofibroblastic Tumors

Inflammatory myofibroblastic tumor cells.

The FDA has granted approval to crizotinib (Xalkori®, Pfizer) for treatment of unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)–positive inflammatory myofibroblastic tumors (IMTs) in adult or pediatric patients one year and older.

“ALK is a receptor tyrosine kinase (RTK) that is known to be oncogenically activated by point mutations within the tyrosine kinase domain, copy-number amplification, or chromosomal translocations” wrote Jennifer Foster, MD, MPH, Director of the Solid Tumor Programs at Texas Children’s Hospital, and colleagues, in their published results of the ADVL0912 trial (NCT00939770), one of the studies on which the approval was based. “These mutations, as well as ALK amplifications, are a promising therapeutic target.”

The safety and efficacy of crizotinib were assessed in two multicenter, single-arm, open-label clinical trials. Fourteen pediatric patients were enrolled in the phase 2 expansion cohort of the ADVL0912 trial, in which patients were given 280 mg/m2 of crizotinib by mouth, twice a day for 28 days. If on Day 28 there was no disease progression or observed unacceptable toxicity, the treatment would be repeated. In addition, seven adult patients were evaluated from the A8081013 (NCT01121588) trial, in which patients received 250 mg of crizotinib twice a day for a 21-day cycle.

The primary end point of both trials was objective response rate. In an evaluation by an independent review committee, significant results were seen for treatment with crizotinib; in the pediatric patients, 12 out of 14 experienced an objective response, and five out of the seven adult patients experienced an objective response.

The most common adverse reactions in ≥35% of pediatric patients treated with 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 common adverse reactions in ≥35% of adult patients treated with crizotinib were vision disorders, nausea, and edema.

“This study indicated strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs,” wrote Carlo Gambacorti-Passerini, MD, Professor of Internal Medicine and Hematology at the University of Milan Bicocca in Italy, and colleagues, in their published results of the A8081013 trial. “The safety profile was consistent with the known safety profile of crizotinib, even with long‐term treatment.”

The recommended crizotinib dose for pediatric patients is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity; in adult patients, the recommended dose is 250 mg orally twice daily until disease progression or unacceptable toxicity.

For More Information

Foster JH, Voss SD, Hall DC, et al (2021). Activity of crizotinib in patients with ALK-aberrant relapsed/refractory neuroblastoma: a Children’s Oncology Group study (ADVL0912). Clin Cancer Res, 27(13):3543-3548. DOI:10.1158/1078-0432.CCR-20-4224

Gambacorti-Passerini C, Orlov S, Zhang L, et al (2018). Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): a phase 1b open-label study. Am J Hematol, 93(5):607-614. DOI:10.1002/ajh.25043 (2020). Crizotinib in treating younger patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma. NLM identifier: NCT00939770. (2021). An investigational drug, crizotinib (PF-02341066), is being studied in tumors, except non-small cell lung cancer, that are positive for anaplastic lymphoma kinase (ALK). NLM identifier: NCT01121588.

Xalkori® (crizotinib) prescribing information (2022). Pfizer. Available at:

US Food and Drug Administration (2022). FDA approves crizotinib for ALK-positive inflammatory myofibroblastic tumor. Available at:

Image credit: Nephron. Licensed under CC BY-SA 3.0

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