Mutation based treatment recommendations from next generation sequencing data: a comparison of web tools.

Interpretation of complex cancer genome data, generated by tumor target profiling platforms, is key for the success of personalized cancer therapy. How to draw therapeutic conclusions from tumor profiling results is not standardized and may vary among commercial and academically-affiliated recommendation tools. We performed targeted sequencing of 315 genes from 75 metastatic breast cancer biopsies using the FoundationOne assay. Results were run through 4 different web tools including the Drug-Gene Interaction Database (DGidb), My Cancer Genome (MCG), Personalized Cancer Therapy (PCT), and cBioPortal, for drug and clinical trial recommendations. These recommendations were compared amongst each other and to those provided by FoundationOne. The identification of a gene as targetable varied across the different recommendation sources. Only 33% of cases had 4 or more sources recommend the same drug for at least one of the usually several altered genes found in tumor biopsies. These results indicate further development and standardization of broadly applicable software tools that assist in our therapeutic interpretation of genomic data is needed. Existing algorithms for data acquisition, integration and interpretation will likely need to incorporate artificial intelligence tools to improve both content and real-time status.
Competing Interests: No conflicts to disclose except for exceptions below: Eric Reiner: Consulting or Advisory Role: BSCI, Surefire Medical; Other Relationship: Sirtex Medical. Sarah Schellhorn Mougalian: Stock and Other Ownership Interests: Gilead Science, Coronado Biosciences, Roche; Research Funding: Genentech. Maysa M. Abu-Khalaf: Research Funding: Novartis, Merck, Clovis Oncology, Pfizer, Genentech/Roche, Merrimack. Lajos Pusztai: Consulting or Advisory Role: Clovis Oncology, Celgene; Honoraria: BioTheranostics, Pfizer; Research Funding: Foundation Medicine, Merck, Genentech.