CHICAGO — The targeted drug crizotinib slowed tumor growth and even eradicated all signs of disease in some children with three aggressive forms of pediatric cancer.
Crizotinib (Xalkori, Pfizer) targets genetic abnormalities in the ALK gene. Those abnormalities are present in up to 95% of anaplastic large cell lymphoma cases (ALCL), half of inflammatory myofibroblastic tumors (IMT) and up to 15% of neuroblastomas.
Yael P. Mosse, MD and colleagues enrolled 70 patients with a median age of 9.9 years whose cancer progressed despite standard therapies. Fifty-seven of the patients were available to be evaluated for the effects of toxicity.
Patients received one of six different doses of crizotinib, ranging from 100 mg/m2 to 365 mg/m2. The doses were administered orally twice a day, and patients remained on treatment for as long as they tolerated it.
Seven of eight patients (88%) with ALCL experienced complete response with no detectable disease, according to study results.
“Our trial shows that crizotinib appears to have a high degree of activity in children with ALCL,” Mosse, assistant professor of pediatrics at The Children’s Hospital of Philadelphia and the University of Pennsylvania, said during a press conference. “A larger ALCL trial is currently in development to move this therapy upfront for newly diagnosed patients.”
The majority of the seven patients with IMT who were enrolled in the trial experienced “substantial benefit,” the researchers said in a press release. The responses — which ranged from tumor shrinkage to complete tumor regression — have lasted up to 2 years, and all patients are still receiving therapy, the researchers said.
Of the 27 patients with neuroblastoma, two had a complete response and eight had no disease progression. Two of the eight patients with proven ALK abnormality experienced a complete response, and some have remained on treatment for more than 2 years without progression. That finding is significant because most heavily pre-treated neuroblastoma patients enrolled in phase 1 trials experience disease progression within 2 months, the researchers said.
“It is remarkable that this targeted oral medication provided such a substantial benefit in these children with highly aggressive cancers, most of whom had already undergone every available therapy,” Mosse said in a press release. “Now that we know more about drivers of some pediatric cancers, we can target those changes and treat patients in a much smarter and potentially safer way.”
For more information:
Mosse Y. Abstract #9500. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: Dr. Mosse reports receiving research funding from Pfizer.