Scientific Reports (Dec 2016)

Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

  • Mitesh J. Borad,
  • Jan B. Egan,
  • Rachel M. Condjella,
  • Winnie S. Liang,
  • Rafael Fonseca,
  • Nicole R. Ritacca,
  • Ann E. McCullough,
  • Michael T. Barrett,
  • Katherine S. Hunt,
  • Mia D. Champion,
  • Maitray D. Patel,
  • Scott W. Young,
  • Alvin C. Silva,
  • Thai H. Ho,
  • Thorvardur R. Halfdanarson,
  • Robert R. McWilliams,
  • Konstantinos N. Lazaridis,
  • Ramesh K. Ramanathan,
  • Angela Baker,
  • Jessica Aldrich,
  • Ahmet Kurdoglu,
  • Tyler Izatt,
  • Alexis Christoforides,
  • Irene Cherni,
  • Sara Nasser,
  • Rebecca Reiman,
  • Lori Cuyugan,
  • Jacquelyn McDonald,
  • Jonathan Adkins,
  • Stephen D. Mastrian,
  • Riccardo Valdez,
  • Dawn E. Jaroszewski,
  • Daniel D. Von Hoff,
  • David W. Craig,
  • A. Keith Stewart,
  • John D. Carpten,
  • Alan H. Bryce

DOI
https://doi.org/10.1038/s41598-016-0021-4
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 12

Abstract

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Abstract DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1–3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.