Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials

Funda Meric-Bernstam, Lauren Brusco, Kenna Shaw, Chacha Horombe, Scott Kopetz, Michael A. Davies, Mark Routbort, Sarina A. Piha-Paul, Filip Janku, Naoto Ueno, David Hong, John De Groot, Vinod Ravi, Yisheng Li, Raja Luthra, Keyur Patel, Russell Broaddus, John Mendelsohn, Gordon Mills

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

Purpose 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. Patients and 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)2753-2762
Number of pages10
JournalJournal of Clinical Oncology
Volume33
Issue number25
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

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Clinical Trials
Genotype
Mutation
Genes
Therapeutics
Investigational Therapies
Patient Preference
Insurance
Pharmaceutical Preparations
Neoplasms
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials. / Meric-Bernstam, Funda; Brusco, Lauren; Shaw, Kenna; Horombe, Chacha; Kopetz, Scott; Davies, Michael A.; Routbort, Mark; Piha-Paul, Sarina A.; Janku, Filip; Ueno, Naoto; Hong, David; De Groot, John; Ravi, Vinod; Li, Yisheng; Luthra, Raja; Patel, Keyur; Broaddus, Russell; Mendelsohn, John; Mills, Gordon.

In: Journal of Clinical Oncology, Vol. 33, No. 25, 01.09.2015, p. 2753-2762.

Research output: Contribution to journalArticle

Meric-Bernstam, F, Brusco, L, Shaw, K, Horombe, C, Kopetz, S, Davies, MA, Routbort, M, Piha-Paul, SA, Janku, F, Ueno, N, Hong, D, De Groot, J, Ravi, V, Li, Y, Luthra, R, Patel, K, Broaddus, R, Mendelsohn, J & Mills, G 2015, 'Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials', Journal of Clinical Oncology, vol. 33, no. 25, pp. 2753-2762. https://doi.org/10.1200/JCO.2014.60.4165
Meric-Bernstam, Funda ; Brusco, Lauren ; Shaw, Kenna ; Horombe, Chacha ; Kopetz, Scott ; Davies, Michael A. ; Routbort, Mark ; Piha-Paul, Sarina A. ; Janku, Filip ; Ueno, Naoto ; Hong, David ; De Groot, John ; Ravi, Vinod ; Li, Yisheng ; Luthra, Raja ; Patel, Keyur ; Broaddus, Russell ; Mendelsohn, John ; Mills, Gordon. / Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 25. pp. 2753-2762.
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abstract = "Purpose 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. Patients and 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. Conclusion 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.",
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T1 - Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials

AU - Meric-Bernstam, Funda

AU - Brusco, Lauren

AU - Shaw, Kenna

AU - Horombe, Chacha

AU - Kopetz, Scott

AU - Davies, Michael A.

AU - Routbort, Mark

AU - Piha-Paul, Sarina A.

AU - Janku, Filip

AU - Ueno, Naoto

AU - Hong, David

AU - De Groot, John

AU - Ravi, Vinod

AU - Li, Yisheng

AU - Luthra, Raja

AU - Patel, Keyur

AU - Broaddus, Russell

AU - Mendelsohn, John

AU - Mills, Gordon

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N2 - Purpose 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. Patients and 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. Conclusion 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.

AB - Purpose 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. Patients and 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. Conclusion 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.

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