Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials

M. J. Overman, V. Morris, B. Kee, D. Fogelman, L. Xiao, C. Eng, A. Dasari, R. Shroff, T. Mazard, K. Shaw, E. Vilar, K. Raghav, I. Shureiqi, L. Liang, Gordon Mills, R. A. Wolff, S. Hamilton, F. Meric-Bernstam, J. Abbruzzese, J. MorrisD. Maru, S. Kopetz

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbermdw073
Pages (from-to)1068-1074
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number6
DOIs
StatePublished - Jun 18 2016
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Biomarkers
Clinical Trials
Standard of Care
Therapeutics
Patient Participation
Phase II Clinical Trials
Clinical Trials, Phase I
CpG Islands
Fluorouracil
Methylation
Multivariate Analysis
Immunohistochemistry
Odds Ratio
Physicians
Phenotype

Keywords

  • Colorectal cancer
  • Molecular
  • Prescreening
  • Screening
  • Targeted

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Overman, M. J., 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. Annals of Oncology, 27(6), 1068-1074. [mdw073]. https://doi.org/10.1093/annonc/mdw073

Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials. / Overman, M. J.; Morris, V.; Kee, B.; Fogelman, D.; Xiao, L.; Eng, C.; Dasari, A.; Shroff, R.; Mazard, T.; Shaw, K.; Vilar, E.; Raghav, K.; Shureiqi, I.; Liang, L.; Mills, Gordon; Wolff, R. A.; Hamilton, S.; Meric-Bernstam, F.; Abbruzzese, J.; Morris, J.; Maru, D.; Kopetz, S.

In: Annals of Oncology, Vol. 27, No. 6, mdw073, 18.06.2016, p. 1068-1074.

Research output: Contribution to journalArticle

Overman, MJ, Morris, V, Kee, B, Fogelman, D, Xiao, L, Eng, C, Dasari, A, Shroff, R, Mazard, T, Shaw, K, Vilar, E, Raghav, K, Shureiqi, I, Liang, L, Mills, G, Wolff, RA, Hamilton, S, Meric-Bernstam, F, Abbruzzese, J, Morris, J, Maru, D & Kopetz, S 2016, 'Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials', Annals of Oncology, vol. 27, no. 6, mdw073, pp. 1068-1074. https://doi.org/10.1093/annonc/mdw073
Overman, M. J. ; Morris, V. ; Kee, B. ; Fogelman, D. ; Xiao, L. ; Eng, C. ; Dasari, A. ; Shroff, R. ; Mazard, T. ; Shaw, K. ; Vilar, E. ; Raghav, K. ; Shureiqi, I. ; Liang, L. ; Mills, Gordon ; Wolff, R. A. ; Hamilton, S. ; Meric-Bernstam, F. ; Abbruzzese, J. ; Morris, J. ; Maru, D. ; Kopetz, S. / Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials. In: Annals of Oncology. 2016 ; Vol. 27, No. 6. pp. 1068-1074.
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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.",
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AU - Morris, V.

AU - Kee, B.

AU - Fogelman, D.

AU - Xiao, L.

AU - Eng, C.

AU - Dasari, A.

AU - Shroff, R.

AU - Mazard, T.

AU - Shaw, K.

AU - Vilar, E.

AU - Raghav, K.

AU - Shureiqi, I.

AU - Liang, L.

AU - Mills, Gordon

AU - Wolff, R. A.

AU - Hamilton, S.

AU - Meric-Bernstam, F.

AU - Abbruzzese, J.

AU - Morris, J.

AU - Maru, D.

AU - Kopetz, S.

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N2 - 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.

AB - 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.

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KW - Molecular

KW - Prescreening

KW - Screening

KW - Targeted

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