Crizotinib Effective in Aggressive Pediatric Tumors

August 2012 Vol 5, No 5, Special Issue ASCO 2012 Payers' Perspective - Pediatric Cancer

Chicago, IL—Crizotinib—which produces robust responses in patients with non–small-cell lung cancer who have abnormalities in the anaplastic lymphoma kinase (ALK) gene—may also have an impact on a number of aggressive pediatric tumors, according to a phase 1 dose-escalation study conducted by the Children’s Oncology Group and reported by lead investigator Yael Mosse, MD, of the Children’s Hospital of Philadelphia, at ASCO 2012.

Crizotinib halted tumor growth in children with anaplastic large-cell lymphoma (ALCL), inflammatory myofibroblastic tumors (IMTs), and aggressive forms of neuroblastoma; in some cases, crizotinib eradicated all signs of cancer, Dr Mosse said.  

Abnormalities in the ALK gene are found in approximately 80% to 95% of patients with ALCL, 50% of those with IMTs, and 10% to 15% of patients with aggressive neuroblastomas.

“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. Now that we know much more about the drivers of some pediatric cancers, we can target those changes and treat patients in a much smarter and potentially safer way,” Dr Mosse said.

This study included 70 children (median age, 10 years) with refractory solid tumors and ALCL. The outcomes by disease were:
•    ALCL: of the 8 patients enrolled, 7 achieved complete responses
•    IMT: of the 7 patients enrolled, 1 had a partial response, 1 had a minor response (tumor shrinkage), and 5 are too early to evaluate
•    Neuroblastoma: of the 35 patients enrolled, 27 were evaluable; of these, 8 patients have known ALK mutations; in this group, 1 had a complete response, 1 had a minor response, and 1 had stable disease. Among the 19 patients whose ALK gene status is unknown, 1 had a complete response and 6 had prolonged stable disease.

The responses tend to be durable, with some patients continuing treatment for >18 months. Compared with ALCL, the benefit of crizotinib is less clear in IMT and in neuroblastoma, although subsets of these patients do appear to respond, Dr Mosse said. These findings have implications beyond these pediatric cancers. “With next-generation sequencing, we may discover that the ALK gene is relevant to multiple human cancers.”

Michael Link, MD, outgoing president of ASCO and a pediatric oncologist himself, said the study has far-ranging implications. “The molecular driver [ALK] is present in very different and sometimes unrelated tumor types, and thus this ALK inhibitor may work in very different cancers,” he predicted.  “We have a glimpse at a new paradigm of understanding cancer and drug development, that it will someday not be sufficient to identify tumors by their histology or organ of origin.”

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