TY - JOUR
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 B.
N1 - Publisher Copyright:
Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
PY - 2015/9/1
Y1 - 2015/9/1
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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U2 - 10.1200/JCO.2014.60.4165
DO - 10.1200/JCO.2014.60.4165
M3 - Article
C2 - 26014291
AN - SCOPUS:84941361474
SN - 0732-183X
VL - 33
SP - 2753
EP - 2762
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -