title: Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials.
abstract: 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 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The study NCT number is NCT01196130.
authors.affiliation: Department of Gastrointestinal Medical Oncology. Electronic address: moverman@mdanderson.org.
authors.forename: M J
authors.initials: MJ
authors.lastname: Overman
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: V
authors.initials: V
authors.lastname: Morris
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: B
authors.initials: B
authors.lastname: Kee
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: D
authors.initials: D
authors.lastname: Fogelman
authors.affiliation: Department of Biostatistics.
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Dasari
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: R
authors.initials: R
authors.lastname: Shroff
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Mazard
authors.affiliation: Department of Sheikh Khalifa Nahyan Ben Zayed Institute for Personalized Cancer Therapy.
authors.forename: K
authors.initials: K
authors.lastname: Shaw
authors.affiliation: Department of Gastrointestinal Medical Oncology; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: E
authors.initials: E
authors.lastname: Vilar
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Raghav
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: I
authors.initials: I
authors.lastname: Shureiqi
authors.affiliation: Department of Biostatistics.
authors.forename: L
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Sheikh Khalifa Nahyan Ben Zayed Institute for Personalized Cancer Therapy; Department of Systems Biology.
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Pathology.
authors.forename: S
authors.initials: S
authors.lastname: Hamilton
authors.affiliation: Department of Sheikh Khalifa Nahyan Ben Zayed Institute for Personalized Cancer Therapy; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: F
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham.
authors.forename: J
authors.initials: J
authors.lastname: Abbruzzese
authors.affiliation: Department of Biostatistics.
authors.forename: J
authors.initials: J
authors.lastname: Morris
authors.affiliation: Department of Pathology.
authors.forename: D
authors.initials: D
authors.lastname: Maru
authors.affiliation: Department of Gastrointestinal Medical Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Kopetz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004608:Eligibility Determination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D018579:Patient Selection
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005472:Fluorouracil
keywords: colorectal cancer; molecular; prescreening; screening; targeted