Lung Cancer Drug Shows Promise against Several Childhood CancersPreliminary results from a phase I clinical trial suggest that the targeted drug crizotinib (Xalkori) may be effective in children with cancer whose tumors harbor genetic alterations in the ALK gene. In some children, the drug caused all signs of the disease to disappear (complete response). Crizotinib is already approved by the Food and Drug Administration to treat patients with lung cancer whose tumors have ALK mutations.
The findings were presented at a press briefing on May 16 in advance of the American Society of Clinical Oncology (ASCO) annual meeting .
Sponsored by the Children's Oncology Group (COG) Phase I Consortium, the study included 70 children whose cancers had progressed on standard treatments. Many had one of three diseases that have been associated with abnormalities in the ALK gene: anaplastic large cell lymphoma (ALCL), neuroblastoma, or a rare type of sarcoma, called inflammatory myofibroblastic tumor (IMT). All of the patients in the trial had seen their disease progress following standard therapy.
When possible, the researchers tested patients' tumors for ALK mutations, but this was not required for enrollment. The study assessed the safety of the drug, which is given as a pill, and established an optimal dose. "Overall, this drug is extremely well tolerated," said Dr. Yael Mossé of Children's Hospital of Philadelphia and the University of Pennsylvania at the press briefing.
Seven of the eight children with ALCL had complete responses. Some remained on the drug without the disease progressing for as long as 18 months. Most cases of ALCL in children are driven by ALK mutations, and COG researchers are developing a new clinical trial to learn how to effectively use crizotinib in children newly diagnosed with that disease.
Of the eight patients with aggressive neuroblastomas, two had complete responses. These two patients, who had documented ALK abnormalities, remained on therapy for 9 months to more than 2 years without the disease progressing, Dr. Mossé noted.
The researchers also reported that the drug had antitumor activity in some patients with IMT. No effective treatments are available for patients with this disease, but about half of IMTs have ALK abnormalities.
This study shows that by understanding "the molecular driver of the tumor, we have the prospect of seeing dramatic responses [in patients]," said ASCO President Dr. Michael P. Link.
The ALK gene appears to be expressed early in development and then shut down after birth, explained Dr. Mossé. This makes the gene an appealing therapeutic target, she added, because it is normally switched off in the body.
Approximately 200 to 250 children are diagnosed with one of these cancers in the United States each year and would be candidates for this treatment based on abnormalities in the ALK gene, Dr. Mossé estimated.
Further reading: "Crizotinib Continues to Show Promise for Some Lung Tumors, Faces Challenge of Drug Resistance"