title: Quantitation of Targetable Somatic Mutations Among Patients Evaluated by a Personalized Medicine Clinical Service: Considerations for Off-Label Drug Use.
abstract: BACKGROUND
  Moffitt Cancer Center's Personalized Medicine Clinical Service (PMCS) reviews somatic next-generation sequencing (NGS) assay results, provides interpretations, and identifies potential therapeutic options. The number of individuals reviewed by our clinical service who are eligible for on-label or off-label drug therapy based on genetic test results has previously not been quantitated. We determined the number of patients harboring an actionable mutation that would qualify a patient for an on-label drug or consideration for off-label drug treatment.
  
  
  METHODS
  The Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling was utilized to identify anticancer agents containing genomic markers in the Indications and Usage section of the drug label. A database containing discrete NGS patient data was queried retrospectively for those drugs and associated genomic mutations included in this study. On-label was defined as those patients who were eligible for a drug based on harboring a targetable mutation in the FDA-approved cancer type. Off-label was defined as those patients who may be considered for a drug based on harboring a targetable mutation in a non-FDA-approved cancer type.
  
  
  RESULTS
  A total of 1072 patients and 1131 NGS results were eligible for study inclusion. Fifty-two patients (4.9%) had results for more than one NGS assay. Seventeen drugs targeting ALK, BRAF, BRCA1/BRCA2, EGFR, or ERBB2 mutations met the study inclusion criteria. Of the entire patient population, 92 (8.6%) unique patients were eligible for at least one on-label drug; off-label use of at least one drug could be considered in 103 (9.6%) unique patients.
  
  
  CONCLUSIONS
  Combining both on-label and off-label opportunities, 175 (16.3%) unique patients had actionable mutations in six genes. Because most patients reviewed by our PMCS have previously treated advanced disease with limited treatment options, identifying additional lines of therapy is of clinical utility.
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Vela
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Knepper
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Gillis
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Walko
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.affiliation: Division of Population Science, DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Hicks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004348:Drug Labeling / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D056687:Off-Label Use; D057285:Precision Medicine / Q000379:methods*; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: off-label drugs; oncology; personalized medicine; pharmacogenomics; precision medicine