Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials.
Abstract
BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical
trials is an active area of investigation, but the factors that determine clinical
trial enrollment following a molecular prescreening program have not been assessed.
PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal
cancer at the MD Anderson Cancer Center were offered screening in the Assessment of
Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility
for companion phase I or II clinical trials with a therapy targeted to an aberration
detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing
panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010
and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and
157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker
selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected
clinical trials was ninefold higher for predefined ATTACC-companion clinical trials
as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P
< 0.001. Factors that correlated positively with trial enrollment in multivariate
analysis were higher performance status, older age, lack of standard of care therapy,
established patient at MD Anderson, and the presence of an eligible biomarker for
an ATTACC-companion study. Early molecular screening did result in a higher rate of
patients with remaining standard of care therapy enrolling on ATTACC-companion clinical
trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1,
P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical
trials resulted in an increase rate of trial enrollment of nonrefractory patients,
the majority of patients enrolled on clinical trials were refractory to standard of
care therapy. Within molecular prescreening programs, tailoring screening for preidentified
and open clinical trials, temporally linking screening to treatment and optimizing
both patient and physician engagement are efforts likely to improve enrollment on
biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is
NCT01196130.
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https://hdl.handle.net/10161/11946Published Version (Please cite this version)
10.1093/annonc/mdw073Publication Info
Overman, MJ; Morris, V; Kee, B; Fogelman, D; Xiao, L; Eng, C; ... Kopetz, S (2016). Utility of a molecular prescreening program in advanced colorectal cancer for enrollment
on biomarker-selected clinical trials. Ann Oncol, 27(6). pp. 1068-1074. 10.1093/annonc/mdw073. Retrieved from https://hdl.handle.net/10161/11946.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
James Abbruzzese
D. C. I. Distinguished Professor of Medical Oncology
My research interests include the clinical study and treatment of pancreatic cancer.

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