Clinical assessment and matching to clinical trials

To assess clinical actionability of mutations, we annotated mutations, copy number alterations, and rearrangements (fusions) using OncoKB (http://oncokb.org). Mutations were classified in a tumor type-specific manner according to the level of evidence that the mutation is a predictive biomarker of drug response. Briefly, mutations were classified as level 1 if they are FDA-approved biomarkers, level 2 if they predict response to standard-of-care therapies, or level 3 if they predict response to investigational agents in clinical trials. Levels 2 and 3 were subdivided according to whether the evidence exists for the pertinent tumor type (2A, 3A) or a different tumor type (2B, 3B). Level 4 mutations were those with compelling biological evidence supporting them as a marker of response to a drug. We did not include ‘TMB-High’ as a predictive biomarker in this study.