Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors

Abstract

In many diseases, molecularly targeted therapies have improved outcomes and decreased treatment-related toxic effects. In oncology, examples such as ERBB2-positive breast cancer¹ and EGFR-mutant lung cancer² have led to excitement about the promise of precision cancer medicine. These and other similar treatment advances typically occurred after years of investigation during which (1) a genomic alteration was identified in a reasonable proportion of patients with a particular diagnosis; (2) the alteration was validated to be a central oncogenic event; (3) the activity of targeted therapy was studied in preclinical models and then in early-phase trials; and (4) clinical trials demonstrated activity of the targeted agent only in cancer subtypes with specific molecular alterations. The essential nature of most pathogenic variants has, therefore, been established only in the context of specific disease subsets. Nevertheless, some oncologists have adopted a precision medicine approach for their patients with recurrent or refractory cancers based on the premise that receipt of matched targeted therapy will have superior clinical activity, regardless of diagnosis or patient characteristics.