Targeted Agent Xalkori May Benefit Children with Anaplastic Lymphoma

The targeted agent Xalkori® (crizotinib) appears to drastically reduce the size of tumors in children with refractory anaplastic large cell lymphoma, according to the results of a phase I study that will be presented at the annual meeting of the American Society of Clinical Oncology in June.

Xalkori is a targeted oral medication that blocks the protein produced by the abnormal anaplastic lymphoma kinase (ALK) gene. It works by works by binding with and inhibiting the action of the enzyme that is produced by the mutated gene. The drug has been approved by the US Food and Drug Administration (FDA) for the treatment of advanced non-small lung cancer that has an abnormal version of the ALK gene, but researchers are now studying its use in other cancers that are driven by the gene as well.

Abnormalities in the ALK gene are common in pediatric cancers and are present in 80 to 95 percent of anaplastic large cell lymphoma (ALCL), 50 percent of inflammatory myofibroblastic tumors (IMT), and 10 to 15 percent of aggressive neuroblastomas.

Researchers from the Children’s Hospital of Philadelphia conducted a study that included 70 children whose cancer had progressed despite all standard therapies. When possible, tumors were tested for ALK abnormalities. Patients received one of six different doses of Xalkori, administered orally, twice a day and remained on the drug as long as it was well tolerated.

The results indicated that the drug stalled tumor growth and, in some cases, eradicated all signs of cancer. Seven out of eight patients with ALCL experienced a complete response, with no detectable disease. These responses have been long lasting—patients have remained on treatment with no progression for as long as 18 months.

The targeted agent appears to offer substantial benefit to patients with refractory neuroblastoma and IMTs as well. Two out of 27 patients with neuroblastoma experienced a complete response and 8 had no disease progression. There were eight neuroblastoma patients with a proven ALK abnormality and 2 of these patients experienced a complete response. Responses in these patients have lasted from 9 months to two years without progression—compared to a typical response period of 1 to 2 months. Patients with IMTs have experienced responses ranging from tumor shrinkage to complete tumor regression and responses have lasted for up to two years—notable because there are no other effective therapies for this disease.

Overall, Xalkori was well-tolerated and mild adverse effects often resolved without changes in dosing.

Based on these results, the researchers concluded that Xalkori induces strong, long-lasting responses in aggressive pediatric cancers. Because of the outstanding responses in the phase I trial, investigators have opted to move directly to a phase III study in an effort to move the therapy to the forefront for newly diagnosed patients. If the promising early results are confirmed in larger trials, Xalkori could become only the second effective targeted agent for pediatric cancers.


Mosse Y, Balis FM, Lim MS, et al. Efficacy of crizotinib in children with relapsed/refractory ALK-driven tumors including anaplastic large cell lymphoma. ASCO 2012; Abstract 9500.

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