Aggressive Pediatric Cancers Respond to ALK Inhibitor

Seven of 8 children with anaplastic large-cell lymphoma in an early-stage study show complete response to crizotinib.

In a phase I trial, children with 3 types of rare and aggressive cancer responded well to crizotinib (Xalkori; Pfizer), which is approved by the U.S. Food and Drug Administration for the treatment of non–small cell lung cancer in patients with mutations in the anaplastic lymphoma kinase (ALK) gene.

ALK is expressed during embryonic development and shut off in normal tissues after birth. This makes it an attractive target for cancer therapies, says Yael Mossé, MD, assistant professor of pediatrics at the Children's Hospital of Philadelphia and the University of Pennsylvania, who led the clinical trial. “When you turn it off, hopefully it won't have other significant effects,” she says.

Early results indicate that this is the case in children whose tumors are driven by ALK abnormalities. The Children's Hospital study was primarily designed to test for safety and to distinguish which patients would benefit from crizotinib at 6 different doses.

Seven of 8 patients with anaplastic large-cell lymphoma (ALCL) and ALK abnormalities had a complete response to the drug. These patients have remained on treatment with no disease progression for up to 18 months.

Among 7 patients with ALK abnormalities and inflammatory myofibroblastic tumors, for which there is no effective therapy available, the majority have seen benefits ranging from tumor shrinkage to complete response.

In 27 neuroblastoma patients, not all of whom could be tested for ALK abnormalities, the outcome is less clear. Two of 7 patients with the abnormality had a complete response and have remained on the therapy for 2 years with no disease progression.

The drug was well tolerated overall, said the researchers, whose results will be presented at the annual meeting of the American Society for Clinical Oncology on June 2.