title: Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials.
abstract: OBJECTIVE
  We report the experience with 2,000 consecutive patients with advanced cancer who underwent testing on a genomic testing protocol, including the frequency of actionable alterations across tumor types, subsequent enrollment onto clinical trials, and the challenges for trial enrollment.
  
  
  METHODS
  Standardized hotspot mutation analysis was performed in 2,000 patients, using either an 11-gene (251 patients) or a 46- or 50-gene (1,749 patients) multiplex platform. Thirty-five genes were considered potentially actionable based on their potential to be targeted with approved or investigational therapies.
  
  
  RESULTS
  Seven hundred eighty-nine patients (39%) had at least one mutation in potentially actionable genes. Eighty-three patients (11%) with potentially actionable mutations went on genotype-matched trials targeting these alterations. Of 230 patients with PIK3CA/AKT1/PTEN/BRAF mutations that returned for therapy, 116 (50%) received a genotype-matched drug. Forty patients (17%) were treated on a genotype-selected trial requiring a mutation for eligibility, 16 (7%) were treated on a genotype-relevant trial targeting a genomic alteration without biomarker selection, and 40 (17%) received a genotype-relevant drug off trial. Challenges to trial accrual included patient preference of noninvestigational treatment or local treatment, poor performance status or other reasons for trial ineligibility, lack of trials/slots, and insurance denial.
  
  
  CONCLUSIONS
  Broad implementation of multiplex hotspot testing is feasible; however, only a small portion of patients with actionable alterations were actually enrolled onto genotype-matched trials. Increased awareness of therapeutic implications and access to novel therapeutics are needed to optimally leverage results from broad-based genomic testing.
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX. fmeric@mdanderson.org.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brusco
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Kenna
authors.initials: K
authors.lastname: Shaw
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Chacha
authors.initials: C
authors.lastname: Horombe
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Mark
authors.initials: M
authors.lastname: Routbort
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sarina A
authors.initials: SA
authors.lastname: Piha-Paul
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: John
authors.initials: J
authors.lastname: De Groot
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Vinod
authors.initials: V
authors.lastname: Ravi
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Russell
authors.initials: R
authors.lastname: Broaddus
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: John
authors.initials: J
authors.lastname: Mendelsohn
authors.affiliation: All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D005240:Feasibility Studies; D005260:Female; D005820:Genetic Testing; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D018579:Patient Selection; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human