ALK Variations and Targeted Therapy in Pediatric Cancers at Cook Children's Medical Center

Purpose: The goal of this project is to report the prevalence of anaplastic lymphoma kinase (ALK) variations in pediatric cancers from a single institution over a six-year period, and to describe the use of small molecules to target these genetic aberrations. Methods: A retrospective chart review was conducted on 82 patients from Cook Children's Medical Center who had tumors sequenced through Foundation Medicine, Inc. from January 1, 2013 to May 1, 2019. Remote sequencing provided results of identified genetic variants and available approved or experimental targeted therapies. In patients harboring ALK variations, the use of available targeted therapies (ALK inhibitors) was analyzed with respect to time to treatment failure (TTF), overall survival (OS), and adverse events (AEs). Results: Of the 82 patients in the study, seven were found to harbor ALK variations, and six patients elected to receive targeted therapy. In three patients, sustained clinical benefit from ALK inhibitors was observed. One patient with relapsed neuroblastoma received crizotinib for 3.9 years. Two other patients, one with refractory neuroblastoma and the other treatment-naïve leiomyosarcoma, were still continued on lorlatinib and crizotinib, each totaling a respective 2.8 years and 217 ongoing days on therapy. None of these patients reported AEs attributed to the targeted therapy, and all three patients were survived at the time of data collection. Conclusion: In certain refractory or relapsed pediatric neoplasms, therapy options remain limited. This study illustrates the use of genomic sequencing to identify ALK as an actionable variant with potential clinical utility.