ASCO 2012 Report – Early, highly promising results for Crizotinib (Xalkori) in three aggressive pediatric cancers

by Bruce Sylvester – In a phase I study presented at ASCO, researchers reported that crizotinib (Xalkori) stalled tumor growth and, in some cases, eradicated all signs of cancer in certain children with aggressive forms of neuroblastoma, anaplastic  large cell lymphoma (ALCL) or inflammatory myofibroblastic tumors (IMT).

Crizotinib targets genetic abnormalities in the ALK gene. It is approved for treatment of adult ALK-driven non-small cell lung carcinoma (NSCLC) in the US and some other countries.

“It’s 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,” said Yael Mosse, MD, assistant professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, USA. “Now that we know more about the drivers of some pediatric cancers, we can target those changes and treat patients in a much smarter, and potentially safer, way.”

Crizotinib could become the second effective molecularly targeted therapy for pediatric cancers, the researchers noted. ALK abnormalities are present in 80 to 95 percent of ALCL cases, half of IMTs and 10 to 15 percent of aggressive neuroblastomas..

Investigators enrolled 70 children whose cancer had progressed after exhaustion of standard therapies. When possible, cancers were tested for ALK abnormalities. Patients received one of six different doses of crizotinib twice daily. They remained on the drug as long as it was well-tolerated.

The researchers reported the following therapeutic results, by disease:

ALCL: 88 percent (7/8) of subjects achieved a complete response, resulting in no detectable disease. Responses have been long-lasting, with subjects who stayed on treatment achieving “no progression” for as long as 18 months.

IMTs: Researchers enrolled 7 subjects with this rare disease into this trial. With treatment, the majority achieved substantial benefit, ranging from tumor shrinkage to complete tumor regression. And responses have lasted for up to two years, with all patients still receiving therapy. Notably, no other available therapies are effective in this disease.

Neuroblastoma: Two of 27 subjects achieved a complete response, and 8 have had no disease progression. Two of eight subjects with a proven ALK abnormality achieved a complete response, and responders have stayed on therapy for between 9 months to more than two years without.

The researchers emphasized that neuroblastoma patients treated with higher doses of crizotinib, sometimes twice the approved adult dose, achieved better responses.

 

The study was funded by Pfizer.