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:10.1038/s41598-016-0021-4

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 AldrichAhmet 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

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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.

Original language	English (US)
Article number	25
Journal	Scientific reports
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41598-016-0021-4
State	Published - 2016

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Borad, M. J., Egan, J. B., Condjella, R. M., Liang, W. S., Fonseca, R., Ritacca, N. R., McCullough, A. E., Barrett, M. T., Hunt, K. S., Champion, M. D., Patel, M. D., Young, S. W., Silva, A. C., Ho, T. H., Halfdanarson, T. R., McWilliams, R. R., Lazaridis, K. N., Ramanathan, R. K., Baker, A., ... Bryce, A. H. (2016). Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers. Scientific reports, 6(1), Article 25. https://doi.org/10.1038/s41598-016-0021-4

Borad, MJ, Egan, JB, Condjella, RM, Liang, WS, Fonseca, R, Ritacca, NR, McCullough, AE, Barrett, MT, Hunt, KS, Champion, MD, Patel, MD, Young, SW, Silva, AC , Ho, TH, Halfdanarson, TR, McWilliams, RR , Lazaridis, KN , Ramanathan, RK, Baker, A, Aldrich, J, Kurdoglu, A, Izatt, T, Christoforides, A, Cherni, I, Nasser, S, Reiman, R, Cuyugan, L, McDonald, J, Adkins, J, Mastrian, SD, Valdez, R, Jaroszewski, DE, Von Hoff, DD, Craig, DW, Stewart, AK, Carpten, JD & Bryce, AH 2016, 'Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers', Scientific reports, vol. 6, no. 1, 25. https://doi.org/10.1038/s41598-016-0021-4

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title = "Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

doi = "10.1038/s41598-016-0021-4",

language = "English (US)",

volume = "6",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

AU - Borad, Mitesh J.

AU - Egan, Jan B.

AU - Condjella, Rachel M.

AU - Liang, Winnie S.

AU - Fonseca, Rafael

AU - Ritacca, Nicole R.

AU - McCullough, Ann E.

AU - Barrett, Michael T.

AU - Hunt, Katherine S.

AU - Champion, Mia D.

AU - Patel, Maitray D.

AU - Young, Scott W.

AU - Silva, Alvin C.

AU - Ho, Thai H.

AU - Halfdanarson, Thorvardur R.

AU - McWilliams, Robert R.

AU - Lazaridis, Konstantinos N.

AU - Ramanathan, Ramesh K.

AU - Baker, Angela

AU - Aldrich, Jessica

AU - Kurdoglu, Ahmet

AU - Izatt, Tyler

AU - Christoforides, Alexis

AU - Cherni, Irene

AU - Nasser, Sara

AU - Reiman, Rebecca

AU - Cuyugan, Lori

AU - McDonald, Jacquelyn

AU - Adkins, Jonathan

AU - Mastrian, Stephen D.

AU - Valdez, Riccardo

AU - Jaroszewski, Dawn E.

AU - Von Hoff, Daniel D.

AU - Craig, David W.

AU - Stewart, A. Keith

AU - Carpten, John D.

AU - Bryce, Alan H.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

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